APSS-33-00: A Multicenter, Pilot Study of Autologous Protein Solution (APS) in Knee Osteoarthritis (OA): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for APSS-33-00: A Multicenter, Pilot Study of Autologous Protein Solution (APS) in Knee Osteoarthritis (OA) (NCT02138890), a randomized na study. The primary outcome is Change From Baseline to 6 Months in Pain Measured With WOMAC Questionnaire (Day 1, Week 2, Month 1, 3 and 6).

2. Clinical Question

The question is framed around pain measured with the WOMAC questionnaire, not around a diagnosis, a radiographic measure, or a time-to-event outcome. A higher WOMAC score indicates worse pain, stiffness, or functional limitation. For the pain subscale, the score ranges from 0, indicating no pain, to 20, indicating maximal pain. A change in score therefore needs to be interpreted with attention to the scale’s direction: a lower score corresponds to less reported pain, while a higher score corresponds to more.

The record also names secondary measures of pain, stiffness, physical function, symptoms, sport and recreational activities, and quality of life. These include WOMAC and KOOS subscales and pain measured with a visual analogue scale. Outcomes were scheduled at several follow-up times from Day 1 through 12 months. The primary question remains narrower: the registry identifies WOMAC pain change through 6 months as the primary outcome, but the posted record does not give results with which to judge the size, precision, or direction of a difference between groups.

3. Trial Design

This was a multicenter, randomized, parallel-group, placebo-controlled pilot study. The registry describes quadruple masking. Randomization is a design feature intended to make treatment assignment independent of measured and unmeasured baseline characteristics on average; it does not guarantee that the groups will be closely balanced in a pilot trial. The allocation ratio and the detailed randomization procedure are not reported in the registry record.

The registered intervention was a single intra-articular APS injection, with saline as the control. The official title describes a double-blind study, while the registry’s masking classification is quadruple. The record does not specify which people were included in the masking classification or provide operational details about how masking was maintained. Therefore, the classification can be reported, but its practical implementation cannot be assessed from this record.

The trial is identified as a pilot study, has phase listed as NA, and is marked completed. The registry records enrollment of 46. It lists a start in 2014-05 and primary completion in 2015-10. These are registry dates, not evidence about the timing or completeness of every follow-up visit. The record describes participants as having knee osteoarthritis and having failed at least 1 conservative therapy.

The primary outcome is WOMAC pain change from baseline to 6 months, with the outcome title also naming assessments at Day 1, Week 2, Month 1, Month 3, and Month 6. Secondary outcomes cover additional patient-reported domains and follow-up times through 12 months. The registry does not give a detailed protocol, the planned analysis model, the allocation ratio, or a sample-size justification. It is therefore not possible to determine from the registry record how the pilot design informed the planned precision or what formal decision criteria were intended for a later study.

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 safety/ITT population analysis population was utilized for this analysis.

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: Patients who have OA in the knee who have failed at least 1 prior conservative OA therapy (e.g. physiotherapy, simple analgesics, intra-articular injection).

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline to 6 Months in Pain Measured With WOMAC Questionnaire (Day 1, Week 2, Month 1, 3 and 6), measured over 6 months.

The primary endpoint is change from baseline to 6 months in pain measured with the WOMAC questionnaire. WOMAC LK 3.1 is described in the registry as a validated tool for knee pain, stiffness, and function. It contains 24 items: 5 pain items, 2 stiffness items, and 17 physical-function items. Each item uses a 5-point Likert response from 0, meaning none or never, to 4, meaning extreme or always. Higher scores indicate worse pain, stiffness, or functional limitation.

The registered pain subscale uses five questions scored from 0 to 4, giving a pain range from 0 to 20. This outcome is useful for describing a patient-reported dimension that is directly relevant to knee osteoarthritis and can be measured repeatedly. Change from baseline expresses how the score differs from a participant’s starting measurement, rather than relying only on a follow-up score. Comparing change between randomized groups can help distinguish the observed course under each assigned intervention, subject to the analysis and completeness of the data.

The scale’s direction matters when reading any estimate: a decrease in WOMAC pain score represents improvement on the scale, while an increase represents worsening. However, the registry record does not report the group means, the mean changes, a between-group estimate, or its uncertainty. It also does not report a threshold for interpreting a change as clinically important. Consequently, the endpoint’s measurement properties and direction can be described, but the trial’s observed primary outcome cannot be interpreted from the registry results available.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The main statistical challenge is not interpreting a reported treatment estimate, because the registry contains no primary outcome analysis. Instead, the record supports an explanation of what analysis would be needed to answer the registered question and what information is absent. The primary outcome is continuous: WOMAC pain is a numerical score, and the registered summary parameter is the mean with standard deviation as the dispersion measure.

What would a group comparison represent?

A mean summarizes the average score or average change in a group. A standard deviation describes how spread out individual observations are around that group mean; it does not describe the precision of the mean itself. To compare randomized groups on the primary endpoint, an analysis would ordinarily report how the mean change in the APS group relates to the mean change in the saline group. The registry record does not report either group’s mean change or the estimated between-group contrast, so none should be inferred.

Change from baseline focuses on within-person movement from an initial score to a later score. A comparison of changes asks whether the average movement differs between the randomized groups. Other valid approaches can model follow-up scores while accounting for baseline, but the registry does not identify which approach was used. The statistical model, covariates, handling of repeated measurements, and any adjustment for baseline are not reported in the registry record.

How should uncertainty be read?

In general, a confidence interval expresses the uncertainty around an estimated quantity under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, while the interval’s location indicates which effect sizes remain compatible with the data and model. A p-value addresses compatibility with a specified null hypothesis under a statistical model; it is not the probability that the null hypothesis is true, nor a measure of clinical importance. No confidence interval or p-value for the primary outcome is reported in the registry record.

For a WOMAC pain contrast, the score direction is important. The registry says higher scores indicate worse pain, stiffness, or functional limitation. Thus an estimate favoring lower pain scores would need to be read in that direction, with the contrast’s coding made clear. The record does not report the coding or a contrast estimate, so no direction can be assigned to an observed result.

What does randomization contribute?

Random assignment is intended to support a fair comparison by reducing systematic differences in treatment assignment. In a pilot study, randomization does not ensure that all baseline characteristics are balanced, particularly when the number of participants is limited. A reported baseline description and analysis plan would help readers assess the groups and the comparison. These details are not reported in the registry record. The record states that the safety/ITT population was used for the primary analysis, but it does not explain its membership or how participants with missing measurements were handled.

Masking can reduce the influence of expectations on care, reporting, or outcome assessment. The registry classifies masking as quadruple, while the official title describes the study as double-blind. It does not identify the masked roles or describe procedures for maintaining masking. This prevents a more detailed assessment of how masking operated.

How do repeated outcomes affect interpretation?

The registered outcomes cover multiple domains and time points. Repeated measurement can describe how outcomes evolve over follow-up, but it also creates analytic choices: researchers may compare a particular visit, model the trajectory across visits, or test an overall pattern. Different choices answer different questions. The registry record does not report the statistical model or clarify how the multiple time points were incorporated into the primary outcome analysis.

Multiplicity arises when several hypotheses or outcomes are examined. In general, testing many outcomes or time points can increase the chance of finding at least one apparently unusual result even when no underlying difference exists. Methods such as prespecifying a primary contrast, adjusting for multiple comparisons, or emphasizing estimation can address aspects of this problem. The registry identifies a primary outcome and lists secondary outcomes, but multiplicity procedures are not reported in the registry record.

What can planning calculations tell readers?

General sample-size planning uses assumptions about the target effect, variability, significance level, allocation, and statistical model to illustrate the information required for a future study. The registry’s stated illustration assumptions include a two-sided significance level of 0.05, equal allocation, and a normal approximation, with effects expressed as stated fractions of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that a treatment effect exists. The registry does not report the trial’s own sample-size justification. Because no primary effect estimate is reported, the observed effect and the resulting planning implications cannot be evaluated from the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and a broad set of secondary outcomes. The registered measures include pain, stiffness, physical function, symptoms, sport and recreational activities, and quality of life. Several measures are scheduled at repeated follow-up times. Examining multiple outcomes and visits creates multiplicity: the more comparisons considered, the more opportunities there are for a result to appear noteworthy by chance. A prespecified hierarchy, adjustment procedure, or clear emphasis on estimation can help readers understand how such results should be interpreted. The registry record does not report a multiplicity strategy.

The primary outcome title includes change from baseline to 6 months and names earlier assessment visits as well. The registry’s note says the primary outcome has several categories or time points and was not reduced to one comparison. The record reports zero analyses. It therefore does not identify a single primary contrast or show how the repeated measures were analyzed. The multiplicity implications cannot be resolved from the record alone.

Missing data are also important for repeated patient-reported outcomes. Participants may miss visits or leave questionnaire items unanswered; different analysis methods make different assumptions about the unobserved values. The registry does not report the amount or pattern of missing outcome data, reasons for missingness, imputation methods, or sensitivity analyses. It is not possible to assess whether the outcome analysis depended on complete follow-up or on assumptions about missing observations.

The primary outcome population is described as the safety/ITT population. The record does not define the population’s membership, provide the number analyzed, or explain how it relates to the randomized groups. The number of participants contributing data at each visit is not reported in the registry record. These omissions limit assessment of the analysis population and the possible effect of missing measurements on the primary comparison.

11. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: meniscus injury (6.7%), bladder cancer (3.2%), nephrolithiasis (3.2%).

The registry reports adverse-event counts separately for the APS injection and control groups. For serious adverse events, the record lists 2 affected among 31 at risk in the APS group and 1 affected among 15 at risk in the control group. For other adverse events, it lists 14 affected among 31 at risk in the APS group and 6 affected among 15 at risk in the control group. Deaths are reported as 0 in each group.

These are descriptive counts, not an adjusted comparison. The registry does not report a statistical test, confidence interval, event timing, severity details beyond the serious classification, or an explanation of how adverse events were collected. The counts should not be interpreted as proving a difference or equivalence in safety between groups. The denominators are the at-risk counts recorded for these outcomes and should not be assumed to represent the number with complete follow-up for every outcome.

The listed serious adverse-event terms include Meniscus Injury at 6.7%, Bladder cancer at 3.2%, and Nephrolithiasis at 3.2%. The registry does not provide enough detail in this listing to establish the relationship of each term to treatment assignment, its timing, or causality. A reported event is not, by itself, evidence that the intervention caused it. The record’s adverse-event figures should be read as reported counts and terms, without extending them to an unreported causal or comparative conclusion.

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

The record establishes that a multicenter, randomized, masked, placebo-controlled pilot study was conducted to evaluate a single APS injection compared with saline in people with knee osteoarthritis who had failed at least 1 conservative therapy. It identifies a patient-reported primary endpoint, WOMAC pain change from baseline to 6 months, and describes the scale and its direction. It also records secondary outcomes across several symptom and function domains and follow-up times.

What the record does not establish is the size or direction of the primary outcome difference. No group-level WOMAC results, between-group estimate, confidence interval, or p-value is reported. The absence of a result cannot be interpreted as evidence of no difference, just as the trial’s randomized design cannot be treated as evidence of a beneficial difference. Neither an efficacy conclusion nor a conclusion of equivalence can be drawn from the registry record’s primary outcome entry.

The same distinction applies to secondary outcomes. They are listed as planned measures, not as reported findings. Without results, it is not possible to say whether pain, stiffness, function, symptoms, or quality of life differed between groups, at which follow-up time, or with what precision. Nor is it possible to assess whether any reported pattern was consistent across measures or visits.

The safety counts provide descriptive information about reported adverse events, but they do not establish causation or a comparative safety profile. Interpretation would require information about event definitions, timing, follow-up, and analysis, in addition to the counts. The serious adverse-event terms are not enough to determine whether events were related to treatment.

In general, a pilot trial can contribute information about feasibility and help shape later research. The particular feasibility goals, decision criteria, and sample-size justification for this study are not reported in the registry record. The enrollment and design alone do not reveal whether the pilot met such goals. The sound conclusion is therefore limited: the record describes the study question, design, outcomes, and adverse-event counts, but it does not report the analyses needed to quantify the primary treatment comparison.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between a registered question and a reported result. The record specifies randomization, a saline control, masking, a continuous primary outcome, and repeated patient-reported measures. Those features describe an intended comparative study. They do not, on their own, supply evidence about the magnitude or precision of a treatment effect.

The pilot designation is relevant to expectations about what a study can establish. A pilot may be designed to assess feasibility or to inform later research, but the registry does not state the specific objectives or decision criteria for this study. With no primary outcome analysis reported, readers cannot determine whether the trial was intended to support a definitive efficacy conclusion, estimate an effect for planning, or meet another objective.

The outcome structure also illustrates why analysis details matter. WOMAC pain was measured repeatedly, while the registry lists other measures across multiple domains and times. Statistical interpretation depends on which contrasts were prespecified, how repeated observations were modeled, how missing measurements were handled, and whether multiplicity was addressed. These details are not reported in the registry record.

The registry’s planning assumptions illustrate a separate statistical role: sample-size calculations can be used to plan future studies, but they are not observed power and cannot substitute for outcome estimates. In this case, the primary result needed to evaluate a planning illustration is not reported. The study’s own sample-size justification is also not reported.

For researchers and readers, the key lesson is to distinguish design information, outcome definitions, and adverse-event counts from inferential results. A completed randomized study can have a clearly identified outcome and still lack a registry-reported treatment estimate. Transparent reporting of estimates, uncertainty, analysis populations, and missing-data methods is necessary to make the intended comparison statistically interpretable.

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 central limitation for interpretation is that the registry record reports no analyses and no numerical primary outcome results. The mean changes, standard deviations, between-group estimate, confidence interval, and p-value are not reported. Without them, the primary comparison cannot be quantified or judged for precision.

The record gives a registered enrollment of 46 but does not report the number analyzed for the primary outcome or the number contributing measurements at each visit. Although it says the safety/ITT population was used, the population is not defined in further detail. The treatment allocation ratio and detailed randomization procedures are also not reported in the registry record.

The primary outcome refers to change through 6 months and names multiple measurement times. The registry indicates that the primary outcome has several categories or time points and was not reduced to one comparison. The statistical model, contrast of interest, and approach to repeated observations are not reported. Multiplicity methods are not reported despite the range of listed outcomes and times.

There is no registry-reported account of missing questionnaire data, missed visits, imputation, or sensitivity analyses. This limits assessment of how the analysis might depend on incomplete follow-up. The record also does not give baseline outcome summaries or other baseline characteristics needed to assess the realized group profiles.

The masking classification is quadruple, while the official title uses double-blind wording. The record does not identify the masked roles or describe how masking was maintained. It also does not report a sample-size justification for the trial, the protocol’s decision criteria, or an explanation of the pilot’s objectives. These are limitations of what can be evaluated from the registry record, not proof that the information was absent from other study materials.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: APSS-33-00: A Multicenter, Pilot Study of Autologous Protein Solution (APS) in Knee Osteoarthritis (OA) — NCT02138890.
• Registry record last updated 2021-02-05; status last verified 2021-01.
• Results first posted 2019-04-12.
• 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.

18. Record Summary

NCT02138890 is a completed multicenter, randomized, parallel-group pilot study of a single intra-articular APS injection compared with saline for knee osteoarthritis. The registry records enrollment of 46, quadruple masking, and phase NA. It describes the target population as patients who had failed at least 1 conservative osteoarthritis therapy.

The primary outcome is change from baseline to 6 months in WOMAC pain. The registry explains that higher WOMAC scores indicate worse pain, stiffness, or functional limitation and gives the pain subscale range as 0 to 20. Secondary measures include pain, stiffness, function, symptoms, sport and recreational activities, and quality of life.

The registry reports zero analyses and does not give a primary outcome estimate or its uncertainty. It lists serious and other adverse-event counts by group, along with deaths and selected serious-event terms. Missing-data methods, multiplicity procedures, the detailed statistical plan, and the trial’s sample-size justification are not reported in the registry record.