This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for SHO-SAIKO-TO for Patients With Chronic Hepatitis C: A Phase II Study (NCT00590564), a na phase 2 study. The primary outcome is To Determine the Effects of Sho-saiko-to on Hepatic Injury in Patients With Chronic Hepatitis C Who Are Intolerant or Have a Specific Contraindication to Interferon-based Therapy..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00590564 |
| Phase | Phase 2 |
| Condition | Hepatitis C |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 42 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Memorial Sloan Kettering Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
People with chronic hepatitis C who were intolerant to interferon-based therapy or had a specific contraindication to it. The registry lists an enrollment of 42; it does not provide further baseline characteristics or describe the enrolled population in detail.
Intervention
Sho-saiko-to (SST), an herbal medicine, given as granules by mouth. The regimen was 2.5grams three times a day every day for 52 weeks, unless unacceptable adverse events occurred or a participant withdrew.
Comparator
There was no separate comparator group in this single-group study. The endpoint description refers to paired comparisons of each participant’s pre-treatment and post-treatment liver biopsies; those within-person measurements are not a randomized control group.
Primary question
Whether participants had an improvement of 2 points or greater in Knodell’s histology activity index (HAI) scores between paired pre-treatment and post-treatment liver biopsies at 52 weeks. The registry record does not report the number of participants who met this response definition.
The clinical question is framed around hepatic injury, rather than a comparison of SST against another treatment. The study description explains that the intended assessment was whether SST might improve liver swelling and injury associated with chronic hepatitis C. The registry identifies people unable to take interferon-based therapy because of intolerance or a specific contraindication, but it does not give further eligibility details or characterize why each participant could not receive that therapy.
Because all participants were assigned to receive SST and no control group is described, the study can document what happened among its participants during treatment and follow-up, but the design cannot by itself separate treatment effects from other explanations for changes in biopsy scores. The endpoint is a change-based response criterion; the registry record does not give the observed response count, the distribution of score changes, or an estimate of uncertainty.
3. Trial Design
The registry describes a phase II, completed, single-group study sponsored by Memorial Sloan Kettering Cancer Center. Enrollment was 42. Allocation is recorded as not applicable, and masking is recorded as none. These design features indicate that the study was not a randomized, blinded comparison between treatment groups. All participants were intended to receive Sho-saiko-to.
The intervention is described as 2.5grams of SST in granules, taken by mouth three times daily every day for 52 weeks. Treatment could end earlier in the event of unacceptable adverse events or participant withdrawal. The registry lists the condition as hepatitis C and identifies the intended population as people with chronic hepatitis C who were intolerant to or had a specific contraindication to interferon-based therapy. More detailed eligibility criteria, recruitment procedures, adherence measures, and the handling of treatment interruptions are not reported in the registry record.
The listed primary endpoint is assessed at 52 weeks and is based on paired pre-treatment and post-treatment liver biopsies. A response is defined as improvement of 2 points or greater according to Knodell’s histology activity index (HAI) scores. The record lists one outcome measure and zero analyses. It does not report an endpoint result, an analysis population, or an account of how many participants completed treatment or had evaluable paired biopsies.
The study start is recorded as 2002-10, primary completion as 2011-02, and status as completed. Those dates describe the registry record’s timing; they do not explain the reasons for the interval between study start and primary completion. The protocol, sample-size justification, interim-analysis plan, and detailed statistical analysis plan are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | All Patients |
|---|---|
| STARTED | 42 |
| COMPLETED | 24 |
| NOT COMPLETED | 18 |
Reasons for not completing this period:
| Reason | All Patients |
|---|---|
| Withdrawal by Subject | 4 |
| Lost to Follow-up | 6 |
| Protocol Violation | 1 |
| Patient Found to be Ineligible | 1 |
| Patient Non-compliance | 6 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | All Patients |
|---|---|---|
| Participants analysed | 42 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 40 |
| Age, Categorical: >=65 years | Participants | 2 |
| Sex: Female, Male: Female | Participants | 13 |
| Sex: Female, Male: Male | Participants | 29 |
6. Primary Endpoint
The registry lists the primary outcome as To Determine the Effects of Sho-saiko-to on Hepatic Injury in Patients With Chronic Hepatitis C Who Are Intolerant or Have a Specific Contraindication to Interferon-based Therapy., measured over 52 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants whose liver-biopsy HAI score improved by 2 points or greater in paired comparisons of pre-treatment and post-treatment biopsies. The stated assessment time is 52 weeks. In plain terms, the endpoint classifies a participant as a responder if the change in the specified histology activity index meets or exceeds that threshold. The registry lists the outcome unit as participants and describes the outcome as a number.
Biopsy-based scores are used to characterize liver tissue findings, so this endpoint focuses on histological injury rather than a symptom report or a virologic measure. A paired assessment compares each participant with their own baseline measurement. In general, using a participant’s baseline can help describe within-person change, but it does not supply the counterfactual comparison that a concurrent control group would provide. Changes could reflect factors other than the intervention, and this design cannot establish how the same participants would have changed without SST.
The registry record does not report the number of responders, the number with paired biopsies, the score distribution, or uncertainty around the response proportion. It also does not describe the biopsy assessment procedures, reader blinding, or how missing or unusable biopsy results were handled. Without the observed endpoint data, the response definition alone does not show whether participants met it or how consistently scores changed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a clinical question and an endpoint, but does not post a primary outcome analysis. It lists one outcome measure and zero analyses. Consequently, there is no reported responder count, response proportion, effect estimate, confidence interval, or p-value for the primary endpoint. The available information cannot establish the magnitude or precision of any change in biopsy scores.
The study enrolled 42 participants, but enrollment is not the same as the number who completed treatment, had both biopsies, or were included in an endpoint analysis. Those counts are not reported in the registry record. This distinction matters because a response count is interpretable only in relation to a clearly defined denominator and analysis population. If some participants lacked an evaluable post-treatment biopsy, the way those participants were handled could affect the reported result; the registry does not describe such handling.
The single-group design also limits causal interpretation. A paired pre-treatment and post-treatment comparison can describe change within participants, but it does not show what would have happened over the same period without SST or under another treatment. General sources of change may include natural variation, changes in other care, measurement variability, and selection of participants who remain under observation. These are design considerations, not claims about what occurred in this study.
Safety information is posted separately from the primary endpoint. The adverse-event record gives an all-patients group with 24 participants at risk for serious events and 3 affected, and 24 at risk for other events and 14 affected. These denominators do not match the overall enrollment of 42, and the record does not explain the difference. The serious-event terms listed as most frequent each have a recorded percentage of 4.2%. These data describe reported events in the registry; without further detail, they do not establish cause, comparative risk, or the timing of events.
The sample-size illustrations associated with the posted results are planning exercises based on an observed effect and specified assumptions. They are not observed power, and they cannot substitute for a reported endpoint analysis. In general, planning calculations describe the sample size that would be needed under assumptions about an effect and a statistical model. Here, a two-arm planning framework does not mirror the actual single-group design, so such illustrations should not be read as evidence from a randomized comparison or as the trial’s original design justification.
Overall, the posted information supports a description of the design, intervention, endpoint definition, and selected safety counts. It does not support a quantitative conclusion about the primary endpoint. The registry record does not report the protocol-level rationale for the sample size, an interim-analysis plan, a complete statistical plan, or details sufficient to assess the endpoint analysis.
9. Statistical Methods Explained
The central statistical feature of this study is its single-group design. Every participant was intended to receive SST, and the primary endpoint uses paired pre-treatment and post-treatment biopsy scores. There is no separate comparator arm. A paired analysis focuses on the change within each participant; a between-group analysis instead compares outcomes across distinct groups. These designs address different questions and produce results with different interpretations.
What does a paired comparison estimate?
In general, a paired comparison uses two measurements from the same participant and evaluates their within-person change. This can account for stable characteristics of that participant when describing change over time. For this endpoint, the registry defines a responder as someone with improvement of 2 points or greater on the Knodell HAI score in paired biopsy comparisons. The registry record does not specify the statistical procedure used to summarize these changes, whether the full score change was analyzed in addition to the responder definition, or how the analysis handled participants without both measurements.
A before-and-after change is not, on its own, a treatment effect isolated from other causes. Without a concurrent control group, the study cannot directly compare observed change with the change that would have occurred over the same period in otherwise similar people not receiving SST. General considerations include the course of the condition over time, other care, measurement variability, and differences between participants who do and do not have follow-up data. These considerations limit causal claims even when a paired change is observed.
What does the response threshold do?
The endpoint converts a score change into a responder classification using a stated threshold: improvement of 2 points or greater. In general, a threshold makes the outcome easier to express as a count of participants meeting a defined criterion. It also discards information about the size and distribution of changes: participants on either side of the threshold are classified differently even if their score changes are close. The record does not explain how the threshold was selected or report results for the underlying score.
For a binary response outcome, an analysis may report the number meeting the criterion and the number assessed, with an uncertainty interval around the response proportion. In general, a confidence interval describes a range of values compatible with the data under the statistical model and sampling assumptions; it communicates precision, not certainty that a particular value is true. No response count, denominator for the primary endpoint, or interval is reported in the registry record, so none can be interpreted for this outcome.
How should the planning illustrations be read?
In general, a sample-size calculation describes how many participants a study would plan to include under specified assumptions about the effect to detect, the significance level, allocation, and statistical model. It is a planning tool, not a result from participants. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. For time-to-event calculations, the stated convention is a total event count; for other calculations, it is participants per arm.
These conventions should not be confused with the actual study design. The trial is recorded as single group, with allocation not applicable, rather than as a two-arm randomized comparison. Thus, a two-arm planning illustration is a hypothetical planning scenario and not a reconstruction of this trial’s design. The registry record does not report the study’s own sample-size justification, so the illustration assumptions do not establish what guided enrollment of 42. They also do not provide observed power. General statistical practice interprets results through estimates and their uncertainty, not by treating post hoc power calculations as evidence that an effect was or was not present.
Why do analysis details matter?
Interpretation depends on which participants contribute to each analysis and how missing data are handled. For a paired biopsy endpoint, participants need an evaluable pre-treatment and post-treatment measurement to contribute a complete pair, unless a specified method addresses missing measurements. The registry record does not report the number with paired biopsies, the rules for excluding or retaining participants, or any imputation method. Without this information, it is not possible to determine whether the endpoint denominator represents all enrolled participants or only a subset.
Other relevant methods include how biopsy scores were assessed, whether readers were blinded to timing, and how adverse events were coded and summarized. These details can affect measurement and reporting. They are not reported in the registry record. The record also contains zero analyses, so no sponsor-reported statistical test or estimate is available to interpret. General explanations of methods therefore clarify what such analyses would mean, but they cannot fill in an analysis that is not posted.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one outcome measure and zero analyses. It does not provide a set of reported endpoint tests from which to assess multiplicity adjustments, nor does it describe a hierarchy of primary and secondary hypotheses. A multiplicity plan for the trial is not reported in the registry record. In general, testing multiple outcomes or time points can increase the chance of at least one apparently unusual result if no adjustment or prioritization is used; that general concern does not establish that multiple tests were conducted in this study.
The primary endpoint requires paired biopsy measurements, but the record does not state how many participants had both measurements or how participants without an evaluable pair were handled. The number of participants analyzed for the endpoint, the analysis population definition, and any missing-data method are not reported in the registry record. These omissions prevent assessment of whether the endpoint analysis included all enrolled participants, only treatment completers, or another group.
In general, missing outcome data can affect both the denominator and the result, particularly when the reason for missingness is related to a participant’s health or treatment experience. No assumption about why data might be missing can be made from the posted record. The protocol, statistical analysis plan, interim-analysis plan, and details of any prespecified handling of missing biopsies or withdrawals are not reported in the registry record. The registry record also does not report whether there were any interim analyses or endpoint changes. As a result, analysis-population choices, missing-data assumptions, and multiplicity control cannot be evaluated from the posted information.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| All Patients | 3 | 24 | 12.5% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| All Patients | 14 of 24 |
Most frequent serious adverse event terms
| Event term | Organ system | All Patients |
|---|---|---|
| Conduction abnormality | Cardiac disorders | 1 of 24 |
| Cellulitis (skin) | Skin and subcutaneous tissue disorders | 1 of 24 |
| Pneumonia | Reproductive system and breast disorders | 1 of 24 |
Most frequent non-serious adverse event terms
| Event term | Organ system | All Patients |
|---|---|---|
| Alanine Aminotransferase (ALT) | Blood and lymphatic system disorders | 11 of 24 |
| Aspartate Aminotransferase (AST) | Blood and lymphatic system disorders | 6 of 24 |
| Hyperglycemia | Metabolism and nutrition disorders | 4 of 24 |
| Neutrophils | Blood and lymphatic system disorders | 3 of 24 |
| Abdominal pain/cramping | Gastrointestinal disorders | 2 of 24 |
| Bilirubin | Hepatobiliary disorders | 2 of 24 |
| Hypoalbuminemia | Metabolism and nutrition disorders | 2 of 24 |
Serious events with the highest arm-level rate: conduction abnormality (4.2%), cellulitis (skin) (4.2%), pneumonia (4.2%).
The adverse-event record lists an all-patients group with 24 participants at risk for serious adverse events and 3 affected. For other adverse events, it lists 24 at risk and 14 affected. These are separate counts for the two categories. The registry also lists conduction abnormality, cellulitis (skin), and pneumonia among the top serious-event terms, each with a recorded percentage of 4.2%.
The counts should be read as registry-reported summaries, not as a comparison with an untreated or alternative-treatment group. The trial has a single group and no control arm. The serious-event denominators are recorded as 24, while overall enrollment is 42; the registry record does not explain the difference. It also does not provide enough detail to determine whether the listed counts represent unique participants, event episodes, or another reporting unit beyond the labels and at-risk counts shown.
In general, an adverse event occurring during a study does not by itself establish that the intervention caused it. The record does not report event timing, severity detail beyond the serious-event classification, relatedness assessments, or a comparative risk estimate. Deaths are not reported in the registry record. The listed terms and percentages therefore describe the posted safety information, but do not establish causality or permit a controlled comparison.
12. What the Result Does, and Does Not, Mean
The record establishes that this completed phase II study evaluated SST in a single group of people with chronic hepatitis C who were intolerant to or had a specific contraindication to interferon-based therapy. It describes a treatment regimen and a primary endpoint based on paired liver biopsies. It also posts selected adverse-event counts. Those details characterize what the study was designed to examine and what safety information was entered in the registry.
The registry does not report the primary endpoint result. It is therefore not possible to state how many participants met the response definition, whether biopsy scores improved overall, or how precise any estimated response would be. An endpoint definition is not an endpoint finding. Similarly, enrollment of 42 does not establish how many participants completed treatment or had evaluable paired biopsies.
Even if a within-person improvement were reported, the single-group design would not show by itself that SST caused that improvement. In general, a concurrent comparison helps distinguish changes associated with an intervention from changes that might occur over time for other reasons. No such control group is described. The record also does not provide enough information about missing outcome data, biopsy assessment, or the full analysis methods to resolve those uncertainties.
The safety counts should likewise be interpreted descriptively. They do not compare SST with another treatment, and they do not establish that reported events were caused by SST. The registry’s serious-event figures use a denominator of 24, while enrollment is 42; the reason for this is not reported in the registry record.
The appropriate conclusion from the posted information is limited: the registry describes a single-group investigation and its intended biopsy-based response criterion, but it does not provide a primary efficacy analysis. No conclusion about the magnitude, precision, or causal interpretation of the primary outcome can be drawn from the endpoint definition and enrollment figure alone.
13. Why This Trial Matters Statistically
This trial illustrates why a clear endpoint definition is not the same as a report of an endpoint result. The registry states how response was to be classified—improvement of 2 points or greater in paired Knodell HAI biopsy scores—but does not report how many participants met that definition. For statistical interpretation, the observed count, its denominator, and an estimate of uncertainty are essential. Without them, the planned question cannot be answered from the posted results.
It also highlights the distinction between within-person change and a controlled treatment comparison. Paired measurements can describe whether participants changed over time. A single-group design, however, does not include a concurrent group that can show how outcomes might have changed without the intervention. This design distinction is central when moving from a descriptive observation to a causal claim.
The record also makes analysis transparency relevant. Enrollment is reported, but the numbers with evaluable paired biopsies and the missing-data approach are not. The adverse-event group denominators are 24, which is different from the stated enrollment of 42, and the reason is not reported in the registry record. Readers therefore need to distinguish the trial’s overall enrollment from the denominators attached to particular safety summaries.
Finally, sample-size planning illustrations are not evidence of observed treatment effects or power. In general, planning calculations depend on assumptions and are meant to inform design. The stated two-arm illustration assumptions do not match the recorded single-group design. The trial therefore provides a useful statistical example of why design, endpoint reporting, analysis population, and safety denominators must be considered together—and why missing results limit interpretation.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main limitation for interpreting the primary outcome is that no analysis is posted. Although the registry defines a biopsy-based response at 52 weeks, it does not report the number of responders, the number assessed, or an estimate of uncertainty. The one listed outcome measure and zero analyses leave the principal clinical question without a reported quantitative answer.
The single-group, unmasked design has no concurrent comparator. Paired biopsies can describe change from baseline, but cannot isolate the effect of SST from time-related changes or other influences. The registry record does not report reader blinding for biopsy assessment, procedures for adjudicating scores, or the statistical method used to analyze the endpoint.
Enrollment was 42, but the number completing treatment, the number with evaluable biopsy pairs, and the endpoint analysis population are not reported in the registry record. The record also does not explain how withdrawals, treatment discontinuations, or missing biopsies were handled. These omissions make it difficult to assess the extent to which outcome data may represent all enrolled participants.
The safety summaries have a denominator of 24 for both serious and other adverse events, and the registry does not explain why this differs from overall enrollment. Event timing, relatedness, and the basis for the term-specific percentages are not described in the information posted. The record does not report deaths.
Further limitations include the absence of a reported protocol-level sample-size justification, detailed statistical analysis plan, interim-analysis plan, and analysis results. The study start and primary-completion dates are recorded, but the registry does not explain the interval between them. These gaps constrain assessment of prespecification, completeness, and the precision of the trial’s findings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: SHO-SAIKO-TO for Patients With Chronic Hepatitis C: A Phase II Study — NCT00590564.
- Registry record last updated 2016-01-15; status last verified 2015-12.
- Results first posted 2016-01-15.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT00590564 is a completed phase II, single-group study sponsored by Memorial Sloan Kettering Cancer Center. It enrolled 42 people with chronic hepatitis C who were intolerant to or had a specific contraindication to interferon-based therapy. Allocation is listed as not applicable, and masking as none.
Participants were to receive Sho-saiko-to granules by mouth at 2.5grams three times daily for 52 weeks, unless unacceptable adverse events or withdrawal occurred. The primary endpoint was a response defined as improvement of 2 points or greater in paired pre-treatment and post-treatment Knodell HAI liver-biopsy scores at 52 weeks.
The registry lists one outcome measure and zero analyses. It does not report a primary outcome result or the number of participants with evaluable paired biopsies. Safety summaries list 3 of 24 participants at risk as affected by serious adverse events and 14 of 24 as affected by other adverse events. The record does not explain the safety denominators or report deaths.