Intra-Articular Injections of Platelet-Rich Plasma in Knee Osteoarthritis: Unique Application Versus Triple Application: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Intra-Articular Injections of Platelet-Rich Plasma in Knee Osteoarthritis: Unique Application Versus Triple Application (NCT02370420), a randomized phase 3 study. The primary outcome is Change in the Western Ontario and McMaster Universities (WOMAC) Ostearthritis Index (Therapeutic Effect).

2. Clinical Question

The central comparison is the number of PRP applications, not PRP versus no PRP: both groups received PRP and were assigned rehabilitation exercises. As a result, the between-group estimate concerns the relative outcomes of these two application schedules in the trial population. It does not isolate the effect of PRP from rehabilitation or from other aspects of care.

The registry describes assessments at baseline and at several follow-up times, while the primary outcome description says only the final measures at 24 weeks are presented as part of the final analysis. The posted primary results therefore should be read as a comparison at that endpoint, not as a complete account of change over every assessment. The registry record does not report a primary analysis of the pattern of outcomes across time.

3. Trial Design

The registry describes a phase 3, randomized, double-masked, parallel-group trial of PRP application schedules for knee osteoarthritis. The sponsor is Universidad Autonoma de Nuevo Leon. The record lists the study as completed, with a start date of 2015-03 and primary completion in 2016-07. Enrollment is listed as 56.

Participants were assigned to a single-application group or a triple-application group. Both groups were also given rehabilitation exercises, and the brief summary says both received information about the approach and were followed as outpatients. The triple-application schedule specified an interval of two weeks between each application. The masking description is recorded as double, but the registry record does not identify which people were masked or describe how masking was maintained.

The outcome measures named in the record are WOMAC, SF-12, and the Visual Analogue Scale (VAS). The registry describes assessment at baseline and at 3 weeks, 6 weeks, 12 weeks, and 24 weeks. The primary outcome is WOMAC, and the posted primary comparison uses final measures at 24 weeks. The secondary outcomes are change in SF-12 and change in VAS, also with the listed follow-up schedule.

The posted outcome summaries report 15 participants in each group for the primary and secondary measures. The relationship between those outcome counts and the enrollment figure is not reported in the registry record. Reasons for missing outcome data, participant flow, and the analysis population are also not reported. Allocation concealment, eligibility criteria beyond the brief description, and the trial’s original sample-size justification are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: After the sign of the informed consent, the patients enrollment were assigned in the group of single injection or triple injection according to a randomization plan.

Overall Study

Reasons for not completing this period:

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 values were obtained only from the patients who completed the study and that were included in the final analysis.

6. Primary Endpoint

The registry lists the primary outcome as Change in the Western Ontario and McMaster Universities (WOMAC) Ostearthritis Index (Therapeutic Effect), measured over Baseline,3 weeks, 6 weeks, 12 weeks, 24 weeks.

The primary endpoint is the change in the Western Ontario and McMaster Universities Osteoarthritis Index, or WOMAC. It is a standardized questionnaire used to assess osteoarthritis symptoms and functional limitations in the knee and hip. Its items cover pain, stiffness, and physical functioning. The registry describes a total score range of 0-96 and states that higher values indicate a worse outcome.

WOMAC is used because it brings several aspects of osteoarthritis burden into a single measure. Pain captures a key symptom, stiffness reflects another reported difficulty, and functional limitation addresses what participants can do. The combined score gives a broad measure of the condition rather than focusing on pain alone. It is also a patient-reported measure, so it reflects participants’ responses to the questionnaire rather than an objective physical test alone.

The outcome title refers to change, but its description says only final measures at 24 weeks are presented as part of the final analysis. The posted group summaries are therefore most safely interpreted as the reported 24-week WOMAC values; the registry record does not provide baseline values or a detailed account of how change was calculated. The difference between group means gives a direct summary of the relative scores at this endpoint. Because lower WOMAC scores indicate a better outcome, the direction of the estimate can be understood against that scale definition, while its uncertainty must also be considered.

7. Results Posted in the Registry

• Triple Application of PRP: mean 22.27 versus 28.53 on control; difference -6.26 (95% CI -18.23 to 5.71), standardized effect d = -0.37; z-test p = 0.305.

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.

Change in the SF-12 Health Survey (Quality of Life)

• 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:
  • Triple Application of PRP: mean 44.74 versus 41.79 on control; difference 2.95 (95% CI -3.42 to 9.32), standardized effect d = 0.33; z-test p = 0.364.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Triple Application of PRP and the control. The interval gives the range of effects that remain compatible with the data.

Change in the Visual Analog Scale (VAS) (Global Pain)

• 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:
  • Triple Application of PRP: mean 3.26 versus 4.46 on control; difference -1.20 (95% CI -3.09 to 0.69), standardized effect d = -0.45; z-test p = 0.214.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Triple Application of PRP and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes are SF-12, a quality-of-life measure, and VAS, a global pain measure. Their posted estimates add context to the WOMAC comparison by showing that the registry considered more than one aspect of participants’ reported outcomes. Across these measures, the numerical directions of the estimated differences are not all the same as the primary estimate. The set of results therefore does not form a single uniform directional pattern.

The secondary results do not replace the primary endpoint. WOMAC is the designated primary outcome, while SF-12 and VAS are secondary outcomes. Their role is to provide additional evidence about related domains, not to provide an independent confirmation simply because they are separate measures. They also should not be combined into one overall claim: they measure different constructs and use different scales.

The registry lists no reported analyses for the secondary outcomes. The posted secondary comparisons are unadjusted, and the record does not state how many hypotheses were considered in the original analysis plan or whether any multiplicity adjustment was prespecified. When several outcomes are examined, the chance of finding a seemingly notable result by chance can increase. General statistical practice therefore gives unadjusted secondary findings less weight than a clearly specified primary comparison, particularly when the analysis plan and multiplicity handling are unavailable.

The secondary outcomes should be read as exploratory context around the primary result. Their uncertainty, the lack of reported analysis details, and the absence of a stated multiplicity strategy limit the strength of conclusions that can be drawn from them. The registry record does not report an integrated analysis that combines the secondary measures with WOMAC or establishes a hierarchy among them.

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

• Change in the SF-12 Health Survey (Quality of Life)
• Change in the Visual Analog Scale (VAS) (Global Pain)

9. Statistical Interpretation

10. Statistical Methods Explained

What does a group mean represent?

A mean is the arithmetic average of participants’ recorded values for an outcome. For WOMAC, the registry reports group means and standard deviations. The mean locates the center of the observed scores, while the standard deviation describes how dispersed individual scores are around that center. A mean difference compares the two group means on the outcome’s original scale, which makes it possible to describe the estimated contrast in WOMAC units.

The comparison is reported as triple application minus single application. A negative value therefore means that the reported mean in the triple-application group is lower than the mean in the single-application group. For WOMAC, the registry states that higher values indicate a worse outcome, so the direction of the estimate can be interpreted using that scale information. This interpretation depends on the outcome definition and does not, by itself, show that the difference is precise or clinically important.

What does a confidence interval add?

A confidence interval expresses uncertainty around an estimated difference. Rather than asking readers to focus only on the single estimate, it gives a range of values compatible with the observed data under the calculation’s assumptions. A narrow interval indicates greater precision than a wide interval. If an interval includes zero for a difference, the data do not exclude the possibility of no difference under that interval procedure. The interval should be considered alongside the point estimate and the outcome’s scale; it is not a guarantee that the true value lies in the reported range.

How should the p-value be read?

A p-value describes how compatible the observed data are with a specified null model, under the assumptions of the statistical procedure. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of a difference. The posted primary comparison gives an unadjusted p-value of 0.305. That value should be read together with the mean difference and its confidence interval, rather than as a standalone decision about the treatment schedules.

The registry record does not report a detailed statistical analysis plan or name the procedure used for a sponsor-conducted primary analysis. The posted comparison summaries are unadjusted. The original handling of baseline values, repeated measurements, missing observations, and departures from model assumptions is not reported in the registry record. Accordingly, an explanatory reading of the summary statistics cannot establish what the trial’s prespecified analysis was.

Why does outcome variability matter?

Individual outcome values vary even when participants receive the same assigned schedule. Greater variability makes it harder to estimate a group contrast precisely, all else being equal. The standard deviations summarize this variability for the posted continuous outcomes. A mean difference can be modest relative to the spread of individual scores, and a small outcome sample can leave considerable uncertainty. The interval around an estimate conveys some of this uncertainty, while the standard deviations help describe the underlying score distributions.

General statistical note: when data are more dispersed than a model assumes, the model may understate uncertainty and produce intervals that are too narrow. The registry does not report an assessment of distributional assumptions or a method for handling unusual observations. No conclusion about those checks can therefore be drawn from the posted record.

What is the role of randomization and masking?

Random assignment is intended to make the assigned groups comparable on average, including with respect to characteristics that may affect outcomes. In an individual trial, randomization does not ensure that every baseline characteristic is balanced, especially when the outcome summaries include a limited number of participants. The registry identifies the allocation as randomized but does not report the sequence-generation or allocation-concealment methods.

The record labels the study double-masked. Masking can reduce the influence of expectations or knowledge of assignment on care, assessment, or reporting, depending on who is masked and how. Those details are not reported in the registry record, so the label alone does not show which potential sources of bias were addressed.

What can be inferred from posted summaries?

Group means, standard deviations, and an estimated mean difference provide a compact description of the recorded outcomes. They do not reveal the distribution of individual scores, the completeness of follow-up, or how measurements from multiple visits were incorporated into an analysis. The primary description lists several assessment times, but says only the final 24-week measures are presented as part of the final analysis. The record does not report a model that uses all visits or an adjusted estimate accounting for baseline values.

General statistical note: repeated measurements from the same participant are correlated. A method that analyzes multiple visits should account for that within-participant relationship; treating every visit as independent could misrepresent uncertainty. The posted primary comparison is a 24-week summary, and the registry record does not describe a repeated-measures analysis.

The unadjusted comparisons also should not be treated as proof of an effect merely because an estimate has a particular sign. Statistical interpretation requires the size of the estimate, its uncertainty, the outcome’s meaning, and the analysis context. In this trial, the primary interval includes zero, and the record provides limited information about the analysis plan and data completeness. These constraints favor a cautious description of the numerical results over a categorical claim.

11. Confidence Intervals and Precision

The primary mean difference is -6.26 WOMAC units, with a confidence interval from -18.23 to 5.712. This interval spans zero and includes values on both sides of it. The point estimate alone therefore gives an incomplete picture: the data are consistent with a lower mean in the triple-application group, but also with a small difference in the opposite direction. The interval includes a range of potentially meaningful contrasts, and the registry record does not specify a threshold for clinical importance.

Precision is shaped by the amount of information in the outcome data and the variability of scores. The posted primary summaries list 15 participants in each group, with standard deviations of 14.0 and 19.07. Those summaries accompany an interval that remains wide enough to leave substantial uncertainty about the size and direction of the comparison.

A confidence interval is not a statement that all values inside it are equally likely, and it does not address possible bias from missing data, measurement, or analysis choices. Its interpretation depends on the method used to calculate it. The registry record does not describe the method or report a confidence level, so the interval is best read as the posted uncertainty range rather than as a complete account of the analysis.

The interval’s inclusion of zero is not evidence that the groups are equivalent. Equivalence would require a prespecified margin and an analysis designed to assess whether differences fall within that margin; those details are not reported in the registry record. The posted estimate is therefore uncertain, rather than proof of sameness or proof of a difference.

12. Planning a Similar Trial: Sample Size

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

The planning figures are participants per arm for 80% power and participants per arm for 90% power. They are not total event counts: this is a continuous-outcome comparison, and the figures describe planned participants in each group under the stated planning setup. The posted planning scenarios use the observed effect as a reference, then consider planning for 75% of the observed effect and 50% of the observed effect. Each scenario gives separate figures for the primary and secondary outcome estimates.

The assumptions listed for these illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. These are planning assumptions for the illustrations; the trial’s own original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column represents the number of participants per arm estimated to give an 80% chance of detecting the specified effect under the planning assumptions if that effect is present. The 90% power column uses a higher target chance of detecting that effect, and therefore calls for more participants per arm under the same assumptions. The figures are planning calculations, not a record of the trial’s achieved ability to detect an effect.

Smaller effects are harder to distinguish from random variation, so the planning figures increase when the target is a smaller fraction of the observed effect. This relationship is useful when considering whether a future study should be designed to detect a more modest difference. These values are not observed power; they are planning illustrations based on the posted effect estimates and stated assumptions.

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 = -6.260; pooled standard deviation σ = 16.728.
2. n = 2 × (1.96 + 0.842)² × 16.728² / -6.260² = 112.1, rounded up to 113 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 <- -6.26                      # observed difference in means
sigma <- 16.7281932676545                     # 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(2370420)
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 = 113 (80% power), 151 (90% power)
 75% of observed effect: n per arm = 200 (80% power), 267 (90% power)
 50% of observed effect: n per arm = 449 (80% power), 601 (90% power)
power.t.test: 113.1 
Simulated power at n = 113 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. Multiplicity, Missing Data and Analysis Populations

The registry identifies WOMAC as the primary outcome and lists SF-12 and VAS as secondary outcomes. It does not report a statistical plan specifying how multiple outcome comparisons were to be handled. In general, evaluating multiple outcomes can increase the chance that at least one comparison appears unusual by chance. Adjustment procedures or a prespecified hierarchy can address that issue, but the registry record does not report whether such a strategy was planned or used. The secondary comparisons are unadjusted, so they warrant less weight than a result from a prespecified primary analysis.

Missing-data handling is also not reported in the registry record. The posted outcome summaries list 15 participants per group, while enrollment is listed as 56. The record does not explain the relationship between these figures, identify how many participants were assessed at each time, or give reasons for unavailable outcomes. It does not state whether any missing values were imputed, whether participants were excluded from analyses, or how withdrawals were handled.

The analysis population is not reported. The record does not say whether the posted comparison followed an intention-to-treat principle, included only participants who completed treatment, or used another population definition. This matters because exclusions after randomization can affect the comparability created by random assignment. Without participant-flow and analysis-population details, readers cannot determine how the posted endpoint summaries relate to all randomized participants.

The description lists assessments at several follow-up times, but the primary endpoint description says only the final measures at 24 weeks are presented as part of the final analysis. The registry record does not report how repeated assessments were modeled or whether baseline values were incorporated. These omissions limit assessment of the statistical plan and the robustness of the posted comparisons.

15. 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 non-serious adverse event terms

The registry reports serious adverse events for 15 participants at risk in each group and records zero serious adverse events in both groups. It also reports zero deaths in each group. For other adverse events, the record reports one affected participant among 15 at risk in each group. No serious adverse event terms are listed.

These counts describe the events recorded in the registry; they should not be treated as proof that no risk exists. The record does not provide event descriptions for the other adverse events, their timing, severity, or whether investigators judged them related to treatment. It also does not report a detailed safety analysis or the method used to collect and classify events.

The groups are small in the posted safety summaries, and uncommon events may not appear in a study of this size. The reported counts should therefore be read as a limited description of observed safety information, not as a definitive comparison of risk between application schedules.

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

The posted primary results describe a numerical difference in 24-week WOMAC scores between the two PRP schedules. The triple-application group had a lower reported mean than the single-application group, and lower WOMAC values indicate a better outcome on the scale. However, the estimated difference is uncertain: its confidence interval includes zero and extends across values in both directions. The unadjusted p-value is 0.305. These data do not establish a clear difference between schedules, but they also do not establish equivalence.

The comparison is specifically between single and triple PRP application, with rehabilitation exercises in both groups. It does not test PRP against no PRP, rehabilitation alone, or another treatment. It cannot determine the effect of PRP itself or separate the contribution of injections from the shared rehabilitation component.

The registry describes several assessment times, but the posted primary analysis description focuses on final measures at 24 weeks. The results do not provide a complete picture of how scores changed over time. Nor does the registry record report enough about missing data, participant flow, the analysis population, or the statistical plan to evaluate all potential sources of uncertainty.

The secondary outcomes supply additional but limited context. They are unadjusted, and the record does not report a multiplicity strategy or formal secondary analyses. Safety counts are also limited and should not be taken as comprehensive evidence about uncommon events. Overall, the results are best understood as an imprecise comparison in this trial’s recorded outcomes, rather than a definitive judgment about treatment benefit, equivalence, or safety.

17. Why This Trial Matters Statistically

This trial illustrates how an active-treatment comparison answers a narrower question than a treatment-versus-no-treatment study. Both groups received PRP and rehabilitation exercises; the randomized contrast concerns the schedule of PRP application. Keeping that distinction clear prevents the between-group estimate from being attributed to PRP in general.

It also shows why a point estimate should not be interpreted on its own. The primary estimate has a direction that can be understood from the WOMAC scale, but its confidence interval includes zero and allows a range of possible differences. Reporting the interval alongside the group means makes the uncertainty visible and discourages an overly categorical reading of the result.

The record provides a useful example of the difference between enrollment and the number of observations represented in posted endpoint summaries. Enrollment is listed as 56, while each outcome summary lists 15 participants in each group. The registry does not explain the relationship. This makes participant flow and missing-data reporting important parts of interpreting a trial, not administrative details separate from the statistical result.

Finally, the secondary measures and planning illustrations demonstrate distinct statistical roles. Unadjusted secondary outcomes offer context but do not carry the same weight as a specified primary endpoint. Planning figures can inform future study design, but they are not a report of power achieved in the completed trial. Careful separation of these roles helps readers interpret the posted evidence without claiming more than the record supports.

18. 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.

Several trial-specific limitations follow from the information recorded. The posted primary outcome summaries include 15 participants in each group, while the registry lists enrollment as 56; participant flow and the explanation for this difference are not reported. The record does not describe missing outcomes, withdrawals, exclusions, or the analysis population. These gaps prevent assessment of whether the endpoint summaries represent all randomized participants or a subset.

The primary outcome is described as change in WOMAC, but the final analysis description says only final measures at 24 weeks are presented. Baseline values and the method used to derive or analyze change are not reported. The listed follow-up times are not accompanied by a reported repeated-measures analysis, so the posted comparison does not convey the full time course.

The statistical analysis plan, original sample-size justification, and analysis assumptions are not reported in the registry record. The record also does not describe allocation concealment, the identity of masked groups, or methods for maintaining masking. Secondary analyses are not reported, and the record does not state how multiplicity was addressed.

The study’s setting and eligibility details are limited in the registry description. Generalizability beyond the described outpatient population cannot be assessed from the posted information alone. Safety reporting gives counts but lacks details on other adverse events, severity, timing, and attribution. These limitations call for cautious interpretation of both outcome and safety summaries.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Intra-Articular Injections of Platelet-Rich Plasma in Knee Osteoarthritis: Unique Application Versus Triple Application — NCT02370420.
• Registry record last updated 2018-02-19; status last verified 2017-08.
• Results first posted 2018-02-19.
• 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.

22. Record Summary

The registry record describes NCT02370420, a completed phase 3, randomized, double-masked, parallel-group trial sponsored by Universidad Autonoma de Nuevo Leon. It compared a single PRP application with three applications at two-week intervals, with rehabilitation exercises in both groups, among patients with knee osteoarthritis.

WOMAC was the primary outcome, with final measures reported at 24 weeks. The posted mean difference for triple versus single application was -6.26 units, with a confidence interval from -18.23 to 5.712 and an unadjusted p-value of 0.305. SF-12 and VAS were listed as secondary outcomes. The record does not report secondary analyses, the original sample-size justification, the analysis population, or missing-data handling.