Spinal Manipulation and Patient Self-Management for Preventing Acute to Chronic Back Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Spinal Manipulation and Patient Self-Management for Preventing Acute to Chronic Back Pain (NCT03581123), a randomized phase 3 study. The primary outcome is Pain Intensity.

2. Clinical Question

3. Trial Design

The registry identifies this as a randomized, double-masked, phase 3 trial using a factorial model. It lists four arms: supported self-management (SSM), spinal manipulation therapy (SMT), a combination of SSM and SMT, and standard medical care (SMC). The trial enrolled 1000 participants. The registry record describes the study population as adults with an acute low back pain flare-up at risk of becoming chronic and disabling, and lists acute pain and mechanical low back pain as conditions.

The treatments lasted up to eight weeks, and participants were to be followed for one year. The primary outcome covers average pain intensity over weeks 1-52, which spans the stated follow-up period. The trial status is completed. The registry records a start date of 2018-11-01 and a primary completion date of 2024-06-12.

The factorial label indicates a design structure involving more than one intervention component, but the registry record does not report the protocol details needed to explain the allocation sequence, masking procedures, or how factorial effects and possible interactions were specified. It also does not report the original sample-size justification, the planned analysis populations, or whether interim analyses were conducted. These details should not be inferred from the label or from the posted outcome data.

The arm sizes differ for the primary outcome: 305 for SSM, 201 for SMT, 193 for the combined arm, and 301 for Medical Care. Numbers with data vary across individual outcomes. That variation means an arm’s sample size for one outcome should not automatically be treated as its size for every analysis. The record names the University of Minnesota as sponsor.

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.

Treatment Adherence Assessment

2-month Follow-up

Reasons for not completing this period:

6-Month Follow-up

Reasons for not completing this period:

12-Month Follow-up

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.

6. Primary Endpoint

The registry lists the primary outcome as Pain Intensity, measured over Average over weeks 1-52.

The primary endpoint is pain intensity, expressed as the mean score on a 0-10 numerical rating scale. A score of 0 denotes no low back pain, while 10 denotes the worst low back pain possible. The endpoint is the average over weeks 1-52, so it represents repeated pain ratings across the follow-up period rather than a single measurement at one visit.

A continuous pain score preserves gradations in reported symptom intensity. Comparing group means can describe differences in average reported pain, while the uncertainty around those means indicates how precisely the estimates are known. The endpoint is relevant to the stated question of whether the treatment approaches differ in longer-term pain intensity after an acute flare-up.

The registry says missing weekly outcomes were multiply imputed. It also says the means were estimated using marginal standardization with adjustment for site, time period, risk of chronicity, and baseline pain intensity. These details matter because the posted mean estimates are not simply unadjusted averages of all recorded weekly scores. The registry record does not report the specific imputation model, the number of imputed datasets, or details of the marginal-standardization procedure.

The registry does not report a threshold for what size of difference on this scale would be considered clinically important. Therefore, the numerical contrasts can be described, but their clinical importance cannot be established from the endpoint results alone.

7. Results Posted in the Registry

• Spinal Manipulation Therapy (SMT): mean 3.00 versus 2.80 on control; difference 0.20 (95% CI -0.08 to 0.48), standardized effect d = 0.12; z-test p = 0.157.
• Combined SSM/SMT: mean 2.80 versus 2.80 on control; difference 0.00 (95% CI -0.28 to 0.28), standardized effect d = 0.00; z-test p = 1.000.
• Medical Care (MC): mean 3.00 versus 2.80 on control; difference 0.20 (95% CI -0.08 to 0.48), standardized effect d = 0.11; z-test p = 0.157.

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.

Recovery From Acute/Sub-acute Low Back Pain

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Spinal Manipulation Therapy (SMT): 15.6% (29/186) versus 19.9% (56/282) on control; risk difference -4.3 percentage points (95% CI -11.3 to 2.7), risk ratio 0.79 (0.52–1.18); unadjusted two-proportion z-test p = 0.241.
  • Combined SSM/SMT: 18.6% (33/177) versus 19.9% (56/282) on control; risk difference -1.2 percentage points (95% CI -8.6 to 6.2), risk ratio 0.94 (0.64–1.38); unadjusted two-proportion z-test p = 0.749.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Spinal Manipulation Therapy (SMT) and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Combined SSM/SMT and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants Who Received Care For Low Back Pain

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Spinal Manipulation Therapy (SMT): 35.8% (67/187) versus 29.6% (82/277) on control; risk difference 6.2 percentage points (95% CI -2.5 to 15.0), risk ratio 1.21 (0.93–1.58); unadjusted two-proportion z-test p = 0.159.
  • Combined SSM/SMT: 29.8% (53/178) versus 29.6% (82/277) on control; risk difference 0.2 percentage points (95% CI -8.4 to 8.8), risk ratio 1.01 (0.75–1.34); unadjusted two-proportion z-test p = 0.969.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Spinal Manipulation Therapy (SMT) and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Combined SSM/SMT and the control. The interval gives the range of effects that remain compatible with the data.

Global Improvement

• 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:
  • Spinal Manipulation Therapy (SMT): mean 6.30 versus 6.20 on control; difference 0.10 (95% CI -0.10 to 0.30), standardized effect d = 0.09; z-test p = 0.321.
  • Combined SSM/SMT: mean 6.40 versus 6.20 on control; difference 0.20 (95% CI -0.01 to 0.41), standardized effect d = 0.17; z-test p = 0.063.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Spinal Manipulation Therapy (SMT) and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Combined SSM/SMT and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists a range of secondary outcomes, including recovery, low back pain frequency, care received, medication use, work-related bother, and global improvement. It reports 30 posted secondary outcomes. Detailed values in the record span binary outcomes and a continuous global-improvement measure, but the available summaries are not a complete account of every outcome named. The broad pattern across the reported material does not establish a consistent advantage across all secondary measures.

The primary pain-intensity estimates are close across the four arms, and the sponsor-reported primary comparisons have confidence intervals that include 0. Secondary outcomes offer additional perspectives on recovery, health-care use, and perceived improvement, but they measure different aspects of the study experience. A secondary outcome that differs from the primary endpoint would not by itself overturn the primary result; it would need to be interpreted in light of its definition, analysis, precision, and place in the overall testing plan.

There are multiple secondary outcomes and comparisons, and the registry record does not report a multiplicity adjustment or a hierarchy for interpreting them. When many hypotheses are tested, the chance of observing some apparently notable results by chance can increase. This is a general statistical concern, not evidence that any particular result is erroneous. Unadjusted secondary results therefore carry less weight as confirmatory evidence, especially when the analysis plan and the status of each endpoint are not reported.

The secondary results are best treated as supportive or exploratory descriptions rather than as a single collection of independent confirmations. Readers should consider whether the direction and uncertainty align with the primary outcome, while avoiding selective emphasis on individual findings. The record does not report enough information to assess the complete prespecified role of each secondary endpoint.

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

• Recovery From Acute/Sub-acute Low Back Pain
• Low Back Pain Frequency - Percent of Days Over 12 Months
• Number of Participants Who Received Care For Low Back Pain
• Medication Use - Percent of Months 4-12
• Bothered by Low Back Pain at Work - Percent of Months
• Global Improvement
• Global Improvement
• Global Improvement

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous, and the registry reports a mean for each arm. A mean describes the average score, but it does not show how individual participants’ scores were distributed. The standard error (SE) describes the estimated precision of a mean: smaller SEs generally indicate that the estimated mean is more precise, while larger SEs indicate greater sampling uncertainty. The primary arm means each have an SE of 0.1. An SE is not the same as the standard deviation, which describes variability among individual observations.

What does the adjusted mean represent?

The registry says the primary means were estimated using marginal standardization, with adjustment for site, time period, risk of chronicity, and baseline pain intensity. In general, adjustment accounts for specified variables when estimating or comparing outcomes. Marginal standardization, in general, uses a fitted model to estimate outcomes under a common distribution of covariates, then averages those estimates. This can make comparisons less dependent on differences in those measured covariates. The precise model, coding choices, and standardization details are not reported in the registry record, so the procedure cannot be reproduced from the summary alone.

The registry also says missing weekly outcomes were multiply imputed. In general, multiple imputation fills in missing values using a statistical model and repeats that process across multiple completed datasets to reflect uncertainty about the missing values. Estimates are then combined to account for both within-dataset uncertainty and variation between imputations. This approach depends on modeling assumptions about the missingness and the variables used. The imputation model, number of datasets, and diagnostics are not reported in the registry record. The outcome summary therefore identifies the method but does not allow its assumptions to be assessed fully.

How should the comparisons be understood?

A mean difference is a contrast between two group means. Its sign depends on which group is subtracted from which. In the sponsor-reported analyses, contrasts are labeled as net mean differences for pairs involving Medical Care. The recalculated contrasts use SSM as the reference. The change in reference changes the direction and framing of the contrast, not the underlying outcome scale. These are not interchangeable presentation conventions unless the subtraction order is kept clear.

A confidence interval gives a range of values compatible with the observed data under the analysis and its assumptions. For a mean difference, an interval containing 0 includes no difference among the values consistent with that interval. It also includes nonzero differences, so it should not be read as proof of equality. The width reflects precision: wider intervals indicate less precise estimates than narrower intervals, all else equal. The sponsor-reported primary comparisons and the supplementary recalculations have intervals that include 0.

The sponsor reports an overall ANOVA p-value of 0.16 for the four groups. In general, an ANOVA tests whether the data provide evidence that not all group means are equal; an overall result does not identify which particular groups differ. Pairwise contrasts address specific comparisons, but their interpretation also depends on whether the testing plan accounted for making multiple comparisons. The registry record does not report a multiplicity plan. A p-value is a measure of how incompatible the observed data are with a specified null model, under the analysis assumptions. It is not the probability that the null hypothesis is true, nor does it convey the size or clinical importance of an effect.

The registry labels the trial factorial, but a factorial design label alone does not tell readers how the primary treatment effects were estimated. For example, the record does not specify whether the reported comparisons were intended as component effects, arm-to-arm effects, or both, or how interactions were addressed. The reported ANOVA and net comparisons can be described as posted; further assumptions about their intended role are not justified by the record.

The binary secondary outcomes are reported as participant counts in groups, with additional unadjusted recalculations of risk differences and intervals. In general, a risk difference compares the proportion with an outcome between two groups. A risk-difference interval that includes 0 is compatible with no difference as well as with differences in either direction. The event definitions and analytic details are not fully described in the registry summaries, and the recalculated comparisons should not be confused with adjusted sponsor analyses.

For any analysis, the estimate, its uncertainty, the outcome definition, and the analysis plan all contribute to interpretation. The posted summary provides group estimates and some sponsor-reported tests, but does not report the full protocol or statistical analysis plan. As a result, readers can describe the posted comparisons while remaining cautious about unreported choices, including model specification, missing-data assumptions, and multiplicity handling.

11. Confidence Intervals and Precision

Precision is reflected in how tightly an estimate is bounded by its confidence interval. For the sponsor-reported primary comparisons, the interval for SSM versus Medical Care runs from -0.5 to 0.0, the interval for SMT versus Medical Care runs from -0.3 to 0.3, and the interval for the combined arm versus Medical Care runs from -0.4 to 0.1. All are reported as 95% confidence intervals. Each includes 0, and each also spans values on either side of 0, so the results do not establish an exact absence of difference.

The supplementary recalculations use a different reference group. The SMT-versus-SSM interval is -0.077 to 0.477; the combined-arm-versus-SSM interval is -0.277 to 0.277; and the Medical-Care-versus-SSM interval is -0.077 to 0.477. These intervals likewise include 0. They are unadjusted recalculations based on posted summary statistics and should be distinguished from the sponsor-reported net comparisons.

Confidence intervals describe uncertainty under the statistical method and assumptions used; they do not include every possible source of uncertainty, such as uncertainty from unreported analytic decisions or limitations in outcome measurement. The registry does not report a clinically meaningful difference threshold for the pain scale. It is therefore not possible to determine from these intervals alone whether all values they contain would be considered practically similar or meaningfully different.

Comparisons with narrower intervals are more precise than those with wider intervals, but precision does not establish importance. Likewise, a p-value does not replace an interval: the interval communicates a range of effect sizes, while a p-value addresses compatibility with a particular null hypothesis. Taken together, the primary results place the estimated group contrasts near 0, with intervals that retain uncertainty about the true contrast.

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 sample-size figures are planning illustrations based on the observed effect, not the trial’s original design assumptions. The assumptions used for the illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and detection of the stated fraction of the observed effect. For these continuous and binary comparisons, the figures are participants per arm, not a total across both arms or a count of total events.

The 80% power column gives the number of participants per arm estimated to provide an 80% chance of detecting the specified effect under those planning assumptions, if that effect and the model assumptions are correct. The 90% power column gives the corresponding per-arm estimate for a 90% chance. These are planning probabilities for a future study under specified conditions, not guarantees about what a study will find. They are not observed power.

Rows that plan for 100%, 75%, or 50% of the observed effect ask what sample size would be needed to detect that fraction of the effect estimate. Smaller effects are harder to distinguish from random variation and therefore require more participants. This pattern is especially important when the observed effect is small: a modest change in the assumed effect can produce a much larger planning sample.

The figures should not be read as evidence that the completed trial was adequately or inadequately powered. The original sample-size justification and design assumptions are not reported in the registry record. The observed arm sizes also differ, whereas the planning illustration assumes equal allocation between the two arms. The illustrations are therefore useful for understanding how sample requirements depend on effect size and target power, but they are not a reconstruction of the trial’s design or a verdict on its conduct.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.200; pooled standard deviation σ = 1.624.
2. n = 2 × (1.96 + 0.842)² × 1.624² / 0.200² = 1,035.0, rounded up to 1,035 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.2                      # observed difference in means
sigma <- 1.62397708952485                     # 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(3581123)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 1,035 (80% power), 1,386 (90% power)
 75% of observed effect: n per arm = 1,840 (80% power), 2,464 (90% power)
 50% of observed effect: n per arm = 4,140 (80% power), 5,543 (90% power)
power.t.test: 1036 
Simulated power at n = 1,035 per arm: 0.799 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The sponsor-reported primary results include an overall ANOVA p-value of 0.16 and net mean differences comparing each active-treatment arm with Medical Care. Those reported contrasts are -0.2 for SSM versus Medical Care, 0.0 for SMT versus Medical Care, and -0.2 for the combined arm versus Medical Care, with their respective 95% confidence intervals listed in the outcome results. These are the sponsor’s own posted analyses.

The supplementary recalculations are unadjusted contrasts derived from the posted arm summary statistics. They use SSM as the reference group, rather than Medical Care, and are not the same adjustment or contrast specification as the sponsor-reported analysis. For example, the recalculated mean difference for SMT relative to SSM is 0.2, while the sponsor reports a net difference of 0.0 for SMT relative to Medical Care. Those estimates answer differently framed comparisons and use different methods; their values should not be treated as conflicting versions of the same contrast.

The registry record does not indicate a discrepancy between sponsor results and the recalculation. In general, sponsor-reported analyses are the primary account of the trial’s prespecified analysis when that plan is documented. Here, the statistical analysis plan and original protocol details are not reported in the registry record, so readers can distinguish the posted sponsor results from the simple recalculations without assuming details of the original plan. The recalculated figures add a descriptive cross-check, but do not replace the sponsor’s reported analyses.

15. Multiplicity, Missing Data and Analysis Populations

The registry reports 37 outcome measures and 36 analyses, including a primary endpoint and numerous secondary outcomes. Multiple outcomes and treatment comparisons create a multiplicity question: testing many hypotheses can increase the chance that at least one result appears unusual by chance, even when no underlying effect exists. In general, a prespecified testing hierarchy or adjustment procedure can help control the interpretation of multiple tests.

The registry record does not report whether multiplicity was addressed, which outcomes were designated confirmatory, whether contrasts were ordered in advance, or whether any correction was applied. The sponsor-reported overall ANOVA and pairwise net differences are posted, but the record does not explain how those results fit into a wider testing strategy. Secondary recalculations are explicitly unadjusted, so their p-values should be read as comparisons considered individually, not as multiplicity-controlled evidence.

Missing data are addressed for the primary outcome: missing weekly outcomes were multiply imputed. The record does not report the imputation model, the variables included, the number of imputed datasets, or sensitivity analyses for alternative assumptions. Multiple imputation can account for uncertainty in missing values under its modeling assumptions, but the summary information is not enough to judge whether those assumptions are plausible for this trial.

The analysis population is not reported in the registry record. The record does not say whether the main analysis followed an intention-to-treat principle, how participants with incomplete follow-up were handled in each secondary outcome, or whether exclusions occurred after randomization. Outcome-specific group counts vary, making it important not to assume that every posted analysis used the full randomized population. The original statistical analysis plan, interim analyses, and sample-size rationale are also not reported in the registry record. These omissions limit assessment of whether the posted analyses match the planned analyses and how much weight to place on unreported analytic decisions.

16. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: other surgical/medical procedure (3.5%), cardiac problems (1.6%), gastrointestinal issues (1.3%), lumbar back-related procedure (1.1%), respiratory issue (1.1%).

The adverse-event summary reports serious adverse events among 27 of 298 participants at risk in SSM, 13 of 198 in SMT, 22 of 190 in the combined arm, and 22 of 296 in Medical Care. Deaths are recorded as 0 in each arm. The registry also reports counts for other adverse events: 93 of 298 in SSM, 63 of 198 in SMT, 63 of 190 in the combined arm, and 82 of 296 in Medical Care.

These counts describe participants with reported events in the registry’s safety summary; they do not by themselves establish that an event was caused by a treatment. The record lists the most frequently reported serious-event terms as other surgical/medical procedure (3.5%), cardiac problems (1.6%), gastrointestinal issues (1.3%), lumbar back-related procedure (1.1%), respiratory issue (1.1%), and fall or accident (1.0%).

Interpretation depends on event definitions, ascertainment, follow-up, and whether events were judged related to treatment. Those details are not reported in the registry record. The arm counts should therefore be read descriptively, not as adjusted comparisons or as proof of relative safety.

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

The posted primary results describe average pain intensity over weeks 1-52 in four randomized treatment arms. The arm means range from 2.8 to 3.0 on the 0-10 scale, and the sponsor-reported comparisons with Medical Care have 95% confidence intervals that include 0. The estimates place the group contrasts near 0, while the intervals show that the data remain compatible with a range of possible differences.

That pattern does not establish that the approaches are equivalent. A conclusion of equivalence or noninferiority would require a defined margin and a suitable prespecified analysis; neither is reported in the registry record. Nor do these results establish that a treatment works or does not work. They describe the observed estimates and their uncertainty under the posted analyses.

The primary endpoint addresses average pain intensity. It does not, by itself, capture every aspect of recovery, function, care use, or participant experience. Secondary outcomes provide other measures, but they are numerous and the registry record does not report a multiplicity plan. The results therefore need to be interpreted together with the endpoint definitions, uncertainty, and the limitations of the available analysis details.

The primary outcome is adjusted for site, time period, risk of chronicity, and baseline pain intensity, and missing weekly values were multiply imputed. These methods are relevant to the estimate, but the details needed to assess their assumptions are not reported in the registry record. The summaries also do not report a clinically meaningful difference threshold for the pain scale. Statistical estimates alone cannot determine whether the observed differences matter to participants.

Overall, the record supports a careful description of the trial’s posted pain estimates and their precision. It does not provide enough information to make claims beyond those analyses, such as a definitive treatment ranking, equivalence, or a general conclusion about all outcomes.

18. Why This Trial Matters Statistically

This trial is statistically informative because it compares four approaches in a randomized, double-masked, factorial design and follows a continuous primary outcome across weeks 1-52. The treatment arms include two individual approaches, their combination, and standard medical care. That structure raises useful questions about both arm-to-arm contrasts and intervention components, while also making the exact analysis plan important for interpretation.

The primary result demonstrates why point estimates and uncertainty should be read together. The group means are close, but a point estimate alone cannot establish how precise the contrast is. The sponsor-reported intervals include 0 and span both directions for the pairwise net comparisons. This supports cautious interpretation rather than a definitive ranking or a claim of equality.

The record also illustrates the distinction between a trial’s own reported analysis and a simple recalculation from summary data. The sponsor’s adjusted net comparisons and the recalculated contrasts use different reference groups and methods. Keeping those distinctions visible prevents a mechanical comparison of numbers that do not represent the same estimand.

Finally, the many secondary outcomes make multiplicity and missing analysis details consequential. Without a reported hierarchy, adjustment plan, analysis population, and full missing-data methods, secondary findings are best treated cautiously. The registry record gives a meaningful statistical snapshot, but it does not include all the protocol and analysis information needed to resolve every inferential question.

19. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several trial-specific details needed for a full assessment are not reported in the registry record. These include the original sample-size justification, the target effect used for planning, the planned analysis populations, and the protocol for randomization and masking. Although the record labels the design factorial, it does not explain how factorial effects, interactions, or the four-arm comparisons were specified.

The primary endpoint uses weekly pain ratings, and the record says missing values were multiply imputed. The imputation model, number of datasets, extent and pattern of missingness, and sensitivity analyses are not reported. The primary means are adjusted for specified factors, but the model and marginal-standardization details are not described in enough depth to reproduce the analysis.

The registry record does not report a multiplicity plan despite the broad set of posted outcomes and analyses. It also does not state whether the sponsor-reported comparisons were prespecified or how they were prioritized. The details of secondary endpoint definitions and analysis populations are incomplete in the summary, and participant counts differ across outcomes.

No threshold for a clinically meaningful difference on the pain scale is reported. Consequently, the statistical estimates cannot be translated into a judgment about practical importance using the registry record alone. The safety summary is also descriptive: event definitions, attribution, and ascertainment details are not reported. These limitations do not negate the posted estimates, but they constrain how far their interpretation can extend.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Spinal Manipulation and Patient Self-Management for Preventing Acute to Chronic Back Pain — NCT03581123.
• Registry record last updated 2025-10-16; status last verified 2025-09.
• Results first posted 2025-10-16.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

23. Record Summary

NCT03581123 is a completed, randomized, double-masked, phase 3 trial sponsored by the University of Minnesota. It enrolled 1000 adults with acute low back pain at risk of chronicity and compared supported self-management, spinal manipulation therapy, their combination, and standard medical care. Treatment lasted up to eight weeks, with follow-up for one year.

The primary outcome was average pain intensity over weeks 1-52 on a 0-10 numerical rating scale. The posted arm means were 2.8 for SSM, 3.0 for SMT, 2.8 for the combined arm, and 3.0 for Medical Care. The sponsor-reported overall ANOVA p-value was 0.16; the reported primary comparison intervals include 0. The registry record does not report the original sample-size rationale, a multiplicity plan, or full analysis details for missing data and analysis populations.