A Non-Interventional Study of RAYOS in Adult Patients With Rheumatoid Arthritis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Non-Interventional Study of RAYOS in Adult Patients With Rheumatoid Arthritis (NCT02287610), a registered phase not stated study. The primary outcome is Mean Change in Severity of Morning Stiffness (Using 100mm VAS) From Baseline (Week 0) to Final Follow-Up Visit.

2. Clinical Question

The study’s stated objective was to assess the effectiveness of switching therapy in routine clinical practice. Its primary outcome focused on participants’ ratings of how severe their morning stiffness was, rather than on a direct comparison between two assigned treatment groups. The registry describes the endpoint as a mean change from baseline to final follow-up, with follow-up extending up to 18.7 weeks.

The question is therefore descriptive of change observed among participants with the required paired measurements. It does not, by itself, isolate the effect of RAYOS from changes over time, other aspects of clinical care, or differences between participants who did and did not contribute both measurements. The numerical mean change and its standard deviation are not reported in the registry record, so the magnitude and precision of the observed change cannot be assessed from the record.

3. Trial Design

This was a completed, non-interventional study in adults with active rheumatoid arthritis. The registry describes its objective as evaluating a switch from conventional immediate-release prednisone to delayed-release prednisone, RAYOS, in clinical practice settings. Participants were managed according to standard of care; the record does not describe a randomized allocation or a separate control group. Allocation is not stated in the registry record.

The study record lists enrollment of 75 and identifies Amgen as the sponsor. The recorded start was 2014-11, and primary completion was 2015-10. The study status is completed. These registry entries describe the study as registered; they do not establish how many participants contributed data to every outcome.

The primary outcome was mean change in morning-stiffness severity, measured with a 0 to 100 mm visual analogue scale, from baseline at Week 0 to the final follow-up visit. The timeframe is described as baseline to the last follow-up visit, up to 18.7 weeks. The registry states that visits and assessments were not mandated because this was a non-interventional research initiative. The primary change was calculated only for participants with both baseline and final follow-up measurements.

The record also lists secondary measures covering morning-stiffness duration, patient and physician assessments of disease activity, several disease-activity indices, and European League Against Rheumatism response. It lists 30 outcome measures overall. A sample-size justification, a detailed protocol for participant selection, and a prespecified statistical analysis plan are not reported in the registry record. The outcome descriptions alone do not establish which analyses were planned or how missing observations were handled.

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: In total, 75 participants enrolled in the study, 11 of them did not meet eligibility requirements and therefore were not included.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 56 participants were in the per protocol follow-up analysis set. Mean change in severity of morning stiffness was calculated for participants who had both baseline and follow-up severity of morning stiffness data. For severity of morning stiffness, the mean change from baseline is based on 38 participants.

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.

6. Primary Endpoint

The registry lists the primary outcome as Mean Change in Severity of Morning Stiffness (Using 100mm VAS) From Baseline (Week 0) to Final Follow-Up Visit, measured over Baseline to Last Follow up visit (up to 18.7 weeks).

The primary endpoint is the mean change in severity of morning stiffness from baseline to the final follow-up visit. Severity was rated on a 0 to 100 mm visual analogue scale: 0 corresponds to not severe at all, and 100 corresponds to extremely severe. The endpoint’s timeframe is baseline to the last follow-up visit, up to 18.7 weeks.

A visual analogue scale captures a participant’s rating along a continuum. The mean change summarizes the average difference between the two recorded ratings among participants with both measurements. In general, change scores can describe whether ratings moved toward less or greater severity, but interpretation depends on the scale’s direction and the way change is defined. The registry does not report the numerical mean change, its standard deviation, or a confidence interval, so the actual direction, size, and precision of the primary result cannot be evaluated from the registry record.

The record specifies that the primary measure was calculated only when both baseline and final follow-up severity measurements were available. It states that 38 participants had the paired severity data used for this change calculation. This outcome-specific analysis set is smaller than the per-protocol follow-up analysis set, which included 56 participants. The record does not explain in detail why measurements were unavailable for other participants.

Morning-stiffness severity is one aspect of rheumatoid arthritis symptoms. It is distinct from morning-stiffness duration and from broader measures of disease activity also listed as secondary outcomes. Using it as a primary measure makes the study’s central question specifically about participants’ reported severity ratings, not a complete summary of disease activity or a comparison of treatment strategies.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Mean change is a summary of within-participant change. For each participant with measurements at both time points, the baseline rating is compared with the final rating; the mean then summarizes those individual changes. This is different from comparing the mean at baseline with the mean at follow-up when those means may be based on different participants. In general, paired data preserve the link between each person’s two observations and can account for the fact that measurements from the same person are related.

The registry defines morning-stiffness severity using a 0 to 100 mm visual analogue scale, anchored from not severe at all to extremely severe. The scale gives a common measurement framework, but the average change alone does not show the distribution of individual changes. Some participants may change more than others, and some may change in different directions. The registry identifies standard deviation as the planned description of dispersion, but the numerical standard deviation is not reported in the registry record.

What does the standard deviation describe?

In general, a standard deviation describes how spread out individual observations are around their mean. For a change outcome, it helps convey whether participants’ changes were relatively similar or more varied. It is not the same as the uncertainty in the estimated mean. A confidence interval, when reported, addresses uncertainty about the mean estimate under the assumptions of the analysis. Neither the standard deviation nor a confidence interval for the primary change is reported in the registry record, so the spread and precision cannot be judged from the posted record.

Why does pairing matter?

General statistical reasoning treats repeated measurements on one participant as related, rather than as observations from unrelated groups. A paired analysis uses each participant’s baseline and follow-up values together. This can be useful when the question concerns change within participants. It also means that participants without one of the two required observations cannot contribute to a simple paired change calculation unless a different method is used. The registry explicitly restricts the primary change calculation to participants with both measurements and reports that 38 participants had those data.

What can a confidence interval or p-value add?

In general, a confidence interval gives a range of values compatible with the data and the statistical model, and it conveys uncertainty around an estimate. A p-value measures how compatible the observed data are with a specified null hypothesis under the model; it is not the probability that the null hypothesis is true and does not measure clinical importance. The registry record does not report a primary confidence interval or p-value. A numerical estimate without such information would have limited precision context, while the record does not report the estimate itself.

What does over-dispersion mean in general?

Over-dispersion is a general concern when observed variability is greater than a statistical model assumes. It can make standard errors too small if the model does not account for the extra variability. It is especially relevant to some count or binary outcome models; the primary endpoint in this record is a continuous change score, described by a mean and standard deviation. The registry does not report a model specification or a diagnostic assessment of dispersion, so no claim about over-dispersion in this study can be made.

The registry lists a sample-size planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is described as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the original study was designed with those assumptions. The record does not report a sample-size justification for the non-interventional study, and it does not describe a randomized two-arm design. Because the primary numerical effect is not reported in the registry record, the planning assumptions should not be mistaken for an observed treatment comparison.

The registry lists 30 outcome measures. In general, testing many outcomes can increase the chance of obtaining at least one apparently unusual result when each is tested separately. Methods such as a prespecified primary endpoint, hierarchical testing, or adjustment for multiple comparisons can address that issue, depending on the analysis plan. The registry record does not report a multiplicity strategy or detailed inferential analyses. The outcome list alone cannot show whether or how such methods were used.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Delayed-release Prednisone (RAYOS)")
n   <- c(38)
m   <- c(-5.2)
sp  <- c(27.3)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Delayed-release Prednisone (RAYOS)  38  -5.200  27.300  -14.173  3.773

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 30 outcome measures, including the primary morning-stiffness severity change and secondary measures of stiffness duration, disease-activity assessments, disease-activity indices, and response. When many outcomes are analyzed, there can be multiple opportunities to observe results that appear notable by chance. In general, a prespecified outcome hierarchy or a multiplicity adjustment can help control the interpretation of multiple statistical tests. The registry record does not report a multiplicity strategy, and it lists zero analyses. It is therefore not possible to determine from this record which comparisons, if any, were tested or how multiple testing was addressed.

Missing outcome data are especially relevant because the registry says that study assessments and visits were not mandated. The primary change was calculated only for participants with both baseline and final follow-up severity measurements. The record reports 56 participants in the per-protocol follow-up analysis set and 38 participants with paired severity data for the primary change. These figures describe different analysis populations. The registry does not report a detailed participant flow, reasons for missing measurements, imputation methods, or sensitivity analyses for missing data.

In general, an analysis restricted to complete pairs is straightforward to interpret as an average among participants with both measurements, but its applicability to all enrolled participants depends on how those participants with data compare with those without data. The record does not provide that comparison. It also does not describe whether additional populations were defined for the secondary outcomes. Consequently, findings from any outcome-specific subset would need to be interpreted in light of the available measurements and the missing-data process, which is not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: abdominal pain (1.3%).

The adverse-event record lists 75 participants at risk for the serious-event and other adverse-event fields. It records 1 participant with a serious adverse event and 11 participants with other adverse events. These are descriptive counts in a non-interventional record, not a comparison between randomized groups.

Abdominal Pain is listed as the top serious adverse event term, with a reported value of 1.3%. The record does not establish from these figures whether an event was caused by RAYOS. An event occurring during a study is not, by itself, evidence of a causal relationship to the intervention. No deaths value is reported in the registry record.

These figures should be read as safety reporting for the registry’s stated observation, not as a complete estimate of risk for other populations or treatment settings. The record does not provide additional detail about event timing, severity categories beyond serious versus other adverse events, or causal assessment. It also does not provide a comparative control group from which relative safety could be evaluated. The absence of a reported death count should not be interpreted as confirmation that no deaths occurred; that information is not reported in the registry record.

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

The study addresses a practical question: how morning-stiffness severity was recorded after a switch from immediate-release prednisone to delayed-release prednisone in adults with active rheumatoid arthritis managed in clinical practice. Its primary endpoint is clearly defined as a mean change on a 0 to 100 mm scale, from baseline to final follow-up, among participants with both measurements. That definition makes the intended outcome understandable.

The registry record does not report the numerical mean change or its standard deviation. It therefore does not show the direction or magnitude of the average change, the degree of variation among participants, or the precision of an estimate. It also does not report a primary confidence interval or p-value. No conclusion about the size or statistical uncertainty of the primary result can be drawn from the record.

Even a reported before-and-after change in a non-interventional study would not, on its own, show that the treatment switch caused the change. Without a stated randomized comparison group, other explanations for change over time remain possible. Clinical practice management, participant characteristics, and the natural course of symptoms may also be relevant in general, but their roles are not evaluated in the registry record.

The primary outcome uses only participants with paired measurements, and the registry reports that this was 38 participants, within a per-protocol follow-up analysis set of 56 participants. The record does not explain missing measurements or show whether participants with and without paired data had similar outcomes. Thus, the primary analysis population is narrower than the enrolled population, and its representativeness cannot be assessed from the available information.

The appropriate conclusion is limited: the registry describes the study objective and the way morning-stiffness severity was to be summarized, but it does not report the primary numerical result needed to judge observed change. The design and missing-data information also limit causal and broader-population interpretations.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of how a real-world outcome definition differs from a controlled treatment comparison. The record focuses on change in a participant-reported symptom after a treatment switch in clinical practice. Because assessments and visits were not mandated, the primary analysis depended on which participants had both baseline and final measurements. That feature makes the analysis population and missing-data process important to interpretation, not merely technical details.

The registry distinguishes the per-protocol follow-up analysis set from the smaller set with paired primary-outcome data. That distinction illustrates why enrollment alone does not define the denominator for every outcome. An endpoint may be available only for participants who complete the relevant measurements, and the characteristics of that subset matter when considering whether an average describes the broader enrolled group.

The record also lists many outcomes, spanning symptom ratings and disease-activity measures. In general, multiple outcomes can support a broad clinical description, but they also require care in selecting and interpreting statistical tests. The registry record does not report a multiplicity approach or detailed analyses, so the existence of an outcome list should not be treated as evidence that every measure was analyzed or that every comparison has confirmatory status.

Finally, the record illustrates the difference between a descriptive change and a causal effect. A before-and-after summary can describe what happened in the analyzed participants; it does not create the counterfactual comparison needed to determine what would have happened without the switch. The missing numerical primary result makes even the descriptive magnitude unavailable, while the non-interventional design would still constrain causal conclusions if that estimate were present.

15. 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 affect interpretation. First, the study was non-interventional and the registry does not state an allocation method or describe a separate comparator group. The record therefore does not support a randomized comparison of RAYOS with another treatment. Change from baseline can be described, but it cannot be attributed solely to the treatment switch using the design information reported.

Second, the registry states that visits and assessments were not mandated. Follow-up measurement availability may therefore vary, and the primary change was calculated only for participants with both baseline and final severity ratings. The record reports 38 participants with paired primary outcome data and 56 in the per-protocol follow-up analysis set, but does not report reasons for missing measurements, participant flow, imputation, or sensitivity analyses. The effect of missingness on the observed average cannot be assessed.

Third, the numerical primary mean change and standard deviation are not reported in the registry record. This prevents evaluation of the result’s direction, magnitude, variability, and precision. The record also lists zero analyses and does not report inferential statistics or a multiplicity strategy despite listing 30 outcome measures.

Finally, the registry does not report a sample-size justification, a detailed statistical analysis plan, or enough information to assess the representativeness of the analyzed participants. These limitations are specific to the information recorded and do not establish that additional procedures or analyses were absent; they are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Non-Interventional Study of RAYOS in Adult Patients With Rheumatoid Arthritis — NCT02287610.
• Registry record last updated 2024-12-18; status last verified 2024-11.
• Results first posted 2017-02-03.
• 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.

19. Record Summary

The registry record describes a completed, non-interventional study of switching from conventional immediate-release prednisone to delayed-release prednisone, RAYOS, among adults with active rheumatoid arthritis in clinical practice. Amgen is listed as sponsor. Enrollment is 75; the recorded start is 2014-11, primary completion is 2015-10, and status is completed.

The primary endpoint was mean change in morning-stiffness severity on a 0 to 100 mm visual analogue scale from baseline to final follow-up, up to 18.7 weeks. The record reports a per-protocol follow-up analysis set of 56 participants and states that the primary change was calculated for the 38 participants with measurements at both time points. It does not report the numerical mean change or standard deviation.

The record lists secondary disease-activity and symptom outcomes, 30 outcome measures, and zero analyses. Safety reporting lists 1 participant with a serious adverse event and 11 with other adverse events; Abdominal Pain is the top serious event term at 1.3%. A deaths value is not reported in the registry record. Missing-data methods, multiplicity procedures, and a sample-size justification are also not reported in the registry record.