Effectiveness of Opiate Replacement Therapy Administered Prior to Release From a Correctional Facility - 1: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effectiveness of Opiate Replacement Therapy Administered Prior to Release From a Correctional Facility - 1 (NCT00142935), a randomized na study. The primary outcome is Treatment Engagement.

2. Clinical Question

The clinical question is about treatment engagement during the first 30 days after release, not about the full course of treatment or long-term outcomes. The trial also explored drug use at six-month follow-up interviews and fatal and non-fatal overdose outcomes. These secondary measures address different events and timeframes, so they should not be treated as interchangeable with the primary attendance outcome.

The trial enrolled 87 participants and compared three assigned approaches. The record describes the study purpose as evaluating pre-release initiation of opiate replacement therapy in relation to HIV risk behaviors and drug relapse, as well as comparing short-term payment with no payment for community treatment. The posted primary outcome, however, is clinic attendance within 30 days. Results for HIV risk behaviors are not reported in the registry record.

3. Trial Design

The registry record describes a randomized, parallel-group study with no masking and a total enrollment of 87. The study is marked completed, and the phase is listed as not applicable. The sponsor is The Miriam Hospital. The record gives the study start as 2006-09 and primary completion as 2009-12. The method used to generate the random sequence, conceal assignments, or manage allocation is not reported in the registry record.

Participants were assigned to one of three approaches. The first arm combined pre-release methadone maintenance treatment (MMT), a post-release referral, and payment support. The registry says MMT began 1-30 days before release; the arm description is truncated, so further dosing and treatment details are not reported in the registry record. The second arm arranged entry to a community methadone clinic within 24-48 hours of release and paid treatment costs in full for 12 weeks, then half the costs for the next 12 weeks. The standard-of-care-plus arm did not begin treatment before release or receive study payment, but staff helped participants identify ways to pay, including help with Medicaid applications.

The primary outcome was assessed by methadone clinic chart review among all enrolled participants, according to the registry description. The posted primary counts are 23 of 29 in the pre-release arm, 11 of 28 in the post-release referral-plus-payment arm, and 6 of 30 in the referral-without-study-payment arm. The record labels the groups “as assigned.” It does not report whether the analysis used a formally defined intention-to-treat population, how departures from assigned treatment were handled, or whether outcome assessors were masked.

The design also included secondary outcomes for drug use, fatal overdose, and non-fatal overdose. Follow-up interview outcomes have smaller denominators than the primary attendance outcome. The reason for each difference, and the original sample-size justification or planned analysis details, 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: There were no significant events following participant enrollment and prior to group assignment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: We assessed community methadone treatment clinic attendance of all enrolled participants based on clinic chart review.

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 Treatment Engagement, measured over within 30 days post release of incarceration.

The primary endpoint is treatment engagement, measured as the number of participants who attended their first community methadone clinic appointment within 30 days after release from incarceration. The registry defines success by attendance at that initial appointment. A referral or a plan to enter treatment alone does not meet this definition. The data source was methadone clinic chart review, and the registry says attendance was assessed for all enrolled participants.

This endpoint captures a practical step in linking people leaving incarceration with community treatment. It asks whether the transition resulted in an initial clinic visit during the stated period. It does not measure continued attendance, duration of treatment, medication adherence, or treatment completion. Those outcomes are not reported in the registry record.

The posted counts are 23 participants in the pre-release MMT plus referral and payment group, 11 in the post-release referral and payment group, and 6 in the post-release referral group without study payment. The corresponding group denominators are 29, 28, and 30. The calculated risk differences compare each post-release strategy with the pre-release strategy. Negative values indicate fewer participants meeting the attendance endpoint in the compared post-release group than in the pre-release group. These differences describe the posted data; they do not by themselves establish why the groups differed.

Attendance is a binary outcome: each participant either had or did not have a qualifying initial appointment within 30 days. It offers a direct measure of early engagement, but it is narrower than the broader study aims described in the registry. The relationship between clinic attendance and subsequent drug use, HIV risk behavior, or overdose is not established by this endpoint alone.

7. Results Posted in the Registry

• As Assigned: MMT Referral Post Release + Payment: 39.3% (11/28) versus 79.3% (23/29) on control; risk difference -40.0 percentage points (95% CI -63.4 to -16.7), risk ratio 0.50 (0.30–0.81); unadjusted two-proportion z-test p = 0.002.
• As Assigned: MMT Referral Post Release: 20.0% (6/30) versus 79.3% (23/29) on control; risk difference -59.3 percentage points (95% CI -79.9 to -38.8), risk ratio 0.25 (0.12–0.53); unadjusted two-proportion z-test p = <0.001.

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.

Drug Use

• 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:
  • As Assigned: MMT Referral Post Release + Payment: 50.0% (8/16) versus 24.0% (6/25) on control; risk difference 26.0 percentage points (95% CI -3.7 to 55.7), risk ratio 2.08 (0.89–4.89); unadjusted two-proportion z-test p = 0.087.
  • As Assigned: MMT Referral Post Release: 52.4% (11/21) versus 24.0% (6/25) on control; risk difference 28.4 percentage points (95% CI 1.2 to 55.5), risk ratio 2.18 (0.97–4.90); unadjusted two-proportion z-test p = 0.047.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between As Assigned: MMT Referral Post Release + Payment and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for As Assigned: MMT Referral Post Release than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Fatal Overdose

• 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:
  • As Assigned: MMT Referral Post Release + Payment: 3.6% (1/28) versus 0.0% (0/29) on control; risk difference 3.6 percentage points (95% CI -3.3 to 10.4); unadjusted two-proportion z-test p = 0.305.
  • As Assigned: MMT Referral Post Release: 3.3% (1/30) versus 0.0% (0/29) on control; risk difference 3.3 percentage points (95% CI -3.1 to 9.8); unadjusted two-proportion z-test p = 0.321.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between As Assigned: MMT Referral Post Release + Payment 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 As Assigned: MMT Referral Post Release and the control. The interval gives the range of effects that remain compatible with the data.

Non-fatal Overdose

• 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:
  • As Assigned: MMT Referral Post Release + Payment: 18.8% (3/16) versus 12.0% (3/25) on control; risk difference 6.8 percentage points (95% CI -16.2 to 29.7), risk ratio 1.56 (0.36–6.81); unadjusted two-proportion z-test p = 0.551.
  • As Assigned: MMT Referral Post Release: 9.5% (2/21) versus 12.0% (3/25) on control; risk difference -2.5 percentage points (95% CI -20.4 to 15.4), risk ratio 0.79 (0.15–4.31); unadjusted two-proportion z-test p = 0.788.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between As Assigned: MMT Referral Post Release + Payment 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 As Assigned: MMT Referral Post Release and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes address different questions from initial clinic attendance: drug use at six-month follow-up interviews, fatal overdose within six months after release, and non-fatal overdose at six-month follow-up interviews. Their overall pattern is less clear-cut than the primary attendance finding. The registry’s overall corrected tests for drug use and non-fatal overdose do not report strong evidence of a group difference, while no overall fatal-overdose test is posted. The pairwise recalculations vary in direction and precision.

These outcomes do not simply confirm or contradict the primary result. Clinic attendance is an early engagement measure; drug use and overdose are separate outcomes observed over different periods and, for interview measures, among smaller follow-up groups. A difference in attendance does not by itself imply a difference in later drug use or overdose. Conversely, an uncertain secondary result does not negate the primary attendance pattern.

Unadjusted secondary results carry less weight because multiple outcomes and comparisons create more opportunities for apparently notable findings by chance. The registry record lists six outcome measures and five analyses, but does not report a multiplicity adjustment or a prespecified hierarchy governing interpretation of the secondary outcomes. The reported tests and recalculated comparisons should therefore be regarded as exploratory evidence unless further analysis-plan information is available.

Follow-up denominators are smaller for drug use and non-fatal overdose than for the primary outcome. Without information on why participants are missing from interviews or how missing outcomes were handled, the extent to which these results represent all randomized participants is uncertain. The secondary endpoints can provide context about the study’s broader aims, but their interpretation is constrained by these smaller numbers, sparse events for overdose, and unreported handling of missing data.

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

• Drug Use
• Fatal Overdose
• Non-fatal Overdose

9. Statistical Interpretation

10. Statistical Methods Explained

What is a risk difference? A risk difference subtracts the proportion with an event in one group from the proportion in another group. For these comparisons, the event is attending the first community clinic appointment within 30 days. A negative risk difference means the compared post-release group had a lower observed event proportion than the pre-release group. This measure is expressed on the probability scale and is useful for describing the absolute separation between groups. The posted estimates are -0.400 and -0.593 for the two primary comparisons.

What does a confidence interval describe? A confidence interval expresses uncertainty around an estimated effect under the statistical procedure used. It gives a range of values compatible with the data and method, rather than a guarantee that the true effect lies within that particular interval. The primary pairwise intervals are reported at 95%: -0.634 to -0.167 for referral and payment after release versus the pre-release group, and -0.799 to -0.388 for referral without study payment versus the pre-release group. Both are entirely below zero. The registry record does not specify the interval method used for its overall test; the pairwise estimates and intervals in these comparisons are recalculations from posted group counts.

How should p-values be read? A p-value describes how unusual data at least as incompatible with a specified null hypothesis would be under that hypothesis and the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. The registry reports a corrected chi-squared test across all three primary groups with p < 0.001. The recalculated pairwise p-values are unadjusted and address two separate comparisons with the pre-release group. They are not substitutes for the reported overall test.

What does the corrected chi-squared test assess? A chi-squared test can assess whether categorical outcome distributions differ across groups. The record names the method as “Chi-squared, Corrected” and gives an overall primary p-value, but does not specify the correction or further details of the test. An overall three-group result tests for evidence of a difference somewhere among the groups; by itself it does not identify which pairs differ. The pairwise recalculations address the two comparisons separately.

Why are risk ratios and odds ratios different measures? A risk ratio compares event proportions as a ratio, while an odds ratio compares event odds. Both can describe relative association, but they are not the same quantity, particularly when the event is not rare. The posted primary recalculations include risk ratios of 0.495 and 0.252, with respective intervals of 0.301 to 0.814 and 0.120 to 0.528. They also include odds ratios of 0.169 and 0.065, with respective intervals of 0.052 to 0.547 and 0.018 to 0.232. These are alternative summaries of the same group counts, not additional outcomes or independent evidence.

Why can over-dispersion matter? In general, over-dispersion means that observed variability exceeds what a model assumes. When a model underestimates variability, standard errors can be too small and intervals too narrow. This is a general statistical concern, but the primary outcome is reported as binary counts, and the registry record gives no over-dispersion parameter or model-based analysis. It would not be appropriate to infer that over-dispersion was assessed or present.

What do small event counts imply? In general, an estimate based on few events can be unstable and its interval can be wide. That issue is relevant to the posted overdose outcomes, where fatal overdose counts are 0, 1, and 1 across the assigned groups. Non-fatal overdose counts are also limited, and follow-up interview denominators are smaller than enrollment. These features constrain precision. They do not permit a conclusion that an outcome is absent or that groups are equivalent.

What is the distinction between reported and recalculated analyses? The registry’s reported primary analysis is an overall corrected chi-squared test. The pairwise risk differences, relative measures, intervals, and unadjusted p-values are recalculations from the posted group counts. These calculations do not reproduce a covariate-adjusted or otherwise unspecified sponsor model. The registry record does not report adjusted effect estimates, covariates, model diagnostics, or sensitivity analyses.

All statistical measures describe evidence and uncertainty under defined assumptions. They do not establish the mechanism behind a group difference. Here, randomized assignment is reported, but the sequence-generation and allocation procedures are not. The available record therefore supports a descriptive reading of the assigned-group outcomes and the stated tests, not reconstruction of every design or analysis decision.

11. Confidence Intervals and Precision

Precision is about how narrowly an effect is estimated. The primary recalculated risk differences have 95% confidence intervals from -0.634 to -0.167 for the referral-plus-payment comparison, and from -0.799 to -0.388 for referral without study payment, each versus pre-release MMT plus referral and payment. The full intervals lie below zero, while their widths also show that the exact size of the difference is uncertain.

The point estimates are -0.400 and -0.593. They summarize the observed separation in the groups, but the confidence intervals are more informative about precision than the point estimates alone. The second comparison’s interval extends farther into negative values, but neither interval identifies the reason for the difference. A confidence interval is not a range of individual participant outcomes and does not account for unreported sources of bias or missing-data procedures.

For the secondary outcomes, interval precision is more limited in several comparisons. Drug use and non-fatal overdose were measured at six-month follow-up interviews, with fewer participants represented than in the primary outcome. The fatal overdose counts are sparse. The recalculated intervals for these outcomes include zero in most pairwise comparisons, and the one drug-use comparison with an interval above zero still comes from a secondary analysis subject to uncertainty and multiplicity concerns. This pattern should not be read as proof of no difference.

The registry’s overall primary p-value provides evidence against equal outcome distributions under the reported chi-squared test, but it does not supply an overall effect-size interval. The registry record does not report a confidence interval for that overall test or adjusted pairwise intervals. The recalculated intervals are unadjusted pairwise estimates, so they do not account for making multiple comparisons. Precision should therefore be judged alongside the group counts, follow-up completeness, and the distinction between the overall sponsor analysis and pairwise recalculations.

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 calculation. For the two-arm binary outcomes, the figures mean participants per arm. They do not mean total participants across both arms or total events. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The target effect is set at the stated fraction of the observed effect.

Read the 80% power column as the number of participants per arm estimated to give an 80% chance of detecting the chosen effect under those planning assumptions, if that effect and the assumptions were correct. The 90% power column gives the corresponding planning number for a 90% chance. For example, planning for 100% of the observed primary effect gives 23 participants per arm for 80% power and 30 per arm for 90% power in the referral-plus-payment comparison. Planning for 75% of the observed effect gives 39 and 52 participants per arm, respectively; planning for 50% gives 83 and 110.

The figures are not observed power. They are conditional planning calculations, not an assessment of how much power the completed study achieved. Smaller effects require more participants because they are harder to distinguish from random variation. The same general pattern appears in the other comparisons, though the exact planning counts depend on the outcome and observed effect.

These illustrations do not show that the original study was designed using the observed effects, nor do they establish that the trial’s enrollment was adequate for every outcome. The original sample-size justification, anticipated effect, and design assumptions are not reported in the registry record. The illustrations are especially sensitive to the observed estimates, which can be uncertain in a modest study and in secondary outcomes with smaller follow-up groups.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.793; treatment proportion p₁ = 0.393; average p̄ = 0.593.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6948 = 1.3617.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6345 = 0.5340.
4. n = (1.3617 + 0.5340)² / (-0.4002)² = 22.4, rounded up to 23 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
p0 <- 0.793103448275862                          # control proportion
p1 <- 0.392857142857143                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(142935)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 23 (80% power), 30 (90% power)
 75% of observed effect: n per arm = 39 (80% power), 52 (90% power)
 50% of observed effect: n per arm = 83 (80% power), 110 (90% power)
power.prop.test: 22.4 
Simulated power at n = 23 per arm: 0.820 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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 registry’s own primary analysis is a corrected chi-squared test across all three assigned groups, reported with p < 0.001. This is an overall test of the group outcome distribution. It is not a pairwise estimate and does not state the size of each group difference. The pairwise risk differences and their intervals are recalculated from the posted group counts and compare each post-release strategy with the pre-release strategy.

Those recalculations give unadjusted p-values of 0.002 for referral and payment after release and <0.001 for referral without study payment. Their direction agrees with the primary counts: fewer participants in each post-release comparison group met the attendance endpoint than in the pre-release group. The recalculations are not adjusted for covariates or for multiple comparisons, and the registry record does not report such adjusted pairwise results.

There is no stated discrepancy between the posted results and the recalculations. The registry’s analysis remains the primary account of the sponsor’s own statistical test; the unadjusted recalculations offer a different, pairwise description of the same posted counts. The record does not provide enough methodological detail to reproduce the corrected test or determine whether it incorporated additional analysis choices.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures and five analyses, including the primary attendance outcome and posted secondary outcomes. Several outcomes have comparisons of two groups against the pre-release group, in addition to the overall three-group tests. Repeated testing can raise the chance of at least one apparently notable result even when there is no true difference. The registry record does not report a multiplicity adjustment, a hierarchy of outcomes, or which outcomes were designated as confirmatory before analysis. The recalculated pairwise p-values are explicitly unadjusted and should not be treated as controlling the error rate across all comparisons.

The primary outcome description says clinic attendance was assessed for all enrolled participants using chart review. The primary group denominators sum to the enrollment of 87, but the record does not describe a formal analysis-population definition beyond the as-assigned group labels. Whether the analysis was formally intention-to-treat, and how participants who did not follow their assignment were treated analytically, are not reported in the registry record.

For drug use and non-fatal overdose, the posted follow-up denominators are smaller than the primary denominators. The record does not report reasons for nonparticipation in interviews, the amount or pattern of missingness, imputation methods, or sensitivity analyses. Without these details, it is not possible to determine whether missing outcomes could have affected the observed group comparisons. Clinic chart review is described as the primary data source, but procedures for unavailable records are not reported.

The record also does not report a full statistical analysis plan, the planned handling of protocol deviations, covariate adjustment, subgroup analyses, interim analyses, or a stopping rule. These details should not be inferred from the posted results. Their absence limits assessment of whether the reported analyses were planned in advance and how robust the findings are to alternative analysis choices.

16. 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: fatal overdose (7.1%).

The adverse-event record reports serious adverse events in 0 of 29 participants in the pre-release MMT plus referral and payment group, 2 of 28 in the post-release referral-plus-payment group, and 1 of 30 in the referral-without-study-payment group. For other adverse events, the record lists 10 of 26 at risk in the first group, 8 of 20 in the second, and 8 of 23 in the third. These counts describe the posted safety data; they are not adjusted comparisons, and the registry does not report a statistical test for them.

The registry lists Fatal Overdose as the top serious-event term at 7.1%. It does not report the denominator or how this term relates to the group-level serious-event counts. Separately, the fatal-overdose outcome counts are 0, 1, and 1 across the three groups within six months from release. The deaths field in the adverse-event record is not reported in the registry record. These different safety entries should not be assumed to represent identical definitions or reporting windows.

The safety counts are small, and the record does not provide event narratives, severity grading beyond the serious/non-serious distinction, exposure-adjusted rates, or a detailed attribution assessment. They therefore support a description of recorded events, not a conclusion about comparative safety.

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

The results describe a randomized comparison of three strategies for connecting participants leaving incarceration with community methadone treatment. For the primary endpoint, the pre-release MMT group had more participants with a documented first clinic appointment within 30 days than either group whose MMT referral began after release. The registry’s overall test reports p < 0.001, and the recalculated pairwise risk differences are negative for both post-release comparisons.

That finding is specifically about initial clinic attendance. It does not establish whether participants continued treatment, how long they remained in care, or whether the approaches changed drug use, HIV risk behavior, or longer-term health outcomes. The registry posts some secondary findings, but those outcomes are less precise and have smaller interview denominators or sparse events. The record does not report HIV risk behavior results.

The group differences also do not identify which component of the strategies accounts for the attendance pattern. The arms differed in treatment timing and payment support, and the posted pairwise comparisons do not isolate timing from payment or other aspects of care. The registry record does not report a factorial comparison or adjusted analysis separating these components.

Statistical evidence is not the same as certainty about the exact effect. The confidence intervals describe uncertainty around the recalculated pairwise differences, and the available methods information is limited. The primary attendance result is stronger than the secondary evidence in the registry record, but it should be interpreted within the enrolled population, the stated endpoint definition, and the reported analysis.

These findings are not medical advice and do not establish that any treatment approach works or fails. They are a statistical account of the posted outcomes. Generalizing beyond this study would require information about the participants, settings, implementation, and analysis that is not fully reported in the registry record.

18. Why This Trial Matters Statistically

This trial raises a statistical question that is common in studies of care transitions: the outcome of interest may be a concrete early step, while the broader goals involve later behavior and health events. Here, a first clinic appointment within 30 days is directly measurable through chart review, but it is not equivalent to sustained treatment or to downstream outcomes. Keeping the endpoint definition clear prevents a statistical difference in engagement from being overread as evidence about every later outcome.

The three-arm design also makes the comparison structure important. The registry reports an overall test across all groups, while pairwise recalculations compare each post-release approach with the pre-release approach. Those answer related but distinct questions. The overall test can indicate that the group distributions differ without identifying the specific contrast; pairwise estimates describe contrasts but create a multiplicity issue when several are considered together.

The trial illustrates why effect estimates and intervals matter alongside p-values. The primary differences are substantial in the posted group counts, but the confidence intervals still cover a range of possible effect sizes. Secondary outcomes have less precision, particularly when follow-up groups are smaller or events are sparse. A non-significant result in those circumstances is not evidence of equivalence.

Finally, the registry’s limited reporting of missing-data procedures, allocation details, and the original analysis plan marks a boundary on interpretation. Randomization is reported, but the record does not expose every design and analysis decision needed for a full audit. The distinction between sponsor-reported testing and transparent recalculation from group counts is therefore important for understanding what the posted evidence can and cannot establish.

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.

The enrollment was 87, and several secondary outcomes have smaller denominators than the primary endpoint. Drug use and non-fatal overdose are based on six-month interviews, while the reasons for missing interviews and the handling of missing outcomes are not reported in the registry record. This limits assessment of whether the secondary comparisons represent the full randomized groups.

The intervention descriptions are incomplete in places. The pre-release arm description is truncated, and the full payment arrangements for that arm are not reported in the registry record. The study compares packages of timing, referral, and payment support, so the posted contrasts cannot isolate the contribution of any single component. The record does not report an analysis designed to separate those effects.

Although randomization is stated, the sequence-generation method and allocation concealment procedures are not reported. The record also does not specify whether the primary analysis was formally intention-to-treat, how adherence or protocol deviations were handled, or whether outcome assessment was masked. These omissions limit evaluation of potential bias and reproducibility.

The registry reports an overall corrected chi-squared test for the primary outcome but does not give its test details or an overall effect-size interval. Pairwise recalculations are unadjusted, and no multiplicity correction is reported. The original sample-size justification, planned effect, and prespecified statistical analysis plan are not reported in the registry record. No subgroup, interim-analysis, or sensitivity-analysis results are posted.

Finally, clinic attendance within 30 days is a narrow engagement outcome. Continued treatment, treatment completion, HIV risk behavior results, and longer-term outcomes are not reported in the registry record. Fatal overdose counts are sparse, and the safety listing does not provide enough detail to resolve the relationship between the listed serious-event term and the group-level safety counts.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Effectiveness of Opiate Replacement Therapy Administered Prior to Release From a Correctional Facility - 1 — NCT00142935.
• Registry record last updated 2014-06-06; status last verified 2009-05.
• Results first posted 2014-06-06.
• 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

NCT00142935 is a completed randomized, parallel-group study with no masking and enrollment of 87. It compared pre-release MMT with post-release referral and payment support against two post-release referral strategies, one with payment support and one without study payment. The primary endpoint was attendance at a first community methadone clinic appointment within 30 days after release, assessed by clinic chart review.

Posted attendance counts were 23 of 29 in the pre-release group, 11 of 28 in the post-release referral-plus-payment group, and 6 of 30 in the referral group without study payment. The registry reports an overall corrected chi-squared p-value of <0.001. Pairwise recalculations show negative risk differences for both post-release comparisons, with the stated uncertainty described in the confidence intervals.

Secondary outcomes cover drug use and fatal and non-fatal overdose. Their interpretation is constrained by smaller follow-up groups, sparse events, and unreported missing-data and multiplicity procedures. The record does not report the original sample-size justification or a full statistical analysis plan.