Trial Design and Randomization

This was a single-site, three-arm, parallel-group randomized controlled trial (RCT). The randomization sequence was generated by computer before the start of the trial via simple random allocation to the study conditions. The principal investigator (E.G.), who directed the randomization, was provided with random numbers to assign to a condition, and he never interacted with participants before or after assignment to a condition. Individuals were the unit of randomization. The University of Utah institutional review board approved all procedures. Participants provided informed consent after reviewing an informed consent cover letter with study personnel.

Setting and Participants

The study was conducted in Salt Lake City from October 2015 through October 2016. The hospital where the study took place had historically performed below the national average in patient ratings of their acute pain management when compared to other academic medical centers, prompting providers at this institution to seek new non-opioid options for addressing acute pain. English-speaking adult inpatients (≥18 years) at a public hospital reporting “intolerable pain” or “inadequate pain control” (on the Clinically Aligned Pain Assessment tool,20 a clinical assessment of pain employed at this hospital) were included in this trial. Patients with altered mental status due to delirium, psychosis, or pharmacological sedation as determined by nursing assessment were excluded. Potential participants were screened for eligibility via medical record review and asked by clinical social workers whether they were interested in receiving psychosocial pain management services as part of a research evaluation.

Procedures

Consenting participants (who were pre-randomized to intervention condition via simple random allocation) then privately completed a brief self-report assessment of patient-reported outcomes (PROs), consisting of validated numeric rating scales (0–10) of pain intensity, pain unpleasantness, relaxation, pleasurable body sensations, and desire for opioids. Following this PRO assessment, participants received one of three 15-min psychosocial interventions delivered by a clinical social worker, after which they privately completed the same self-report assessment to assess patient-reported outcomes during the period immediately following the intervention. Social workers and participants were not blinded. Participants were not compensated for their participation.

Interventions

Mindfulness Training

The mindfulness intervention consisted in a single, scripted 15-min training session in focused attention on breathing and body sensations, with concomitant metacognitive monitoring and acceptance of discursive thoughts, negative emotions, and pain. This mindfulness script (see supplementary materials) closely followed a mindfulness induction script validated in prior mindfulness research.21

Hypnotic Suggestion

The suggestion intervention consisted in a single, scripted 15-min self-hypnosis session which invited patients to roll their eyes upward, close their eyes, and breathe deeply, focus on sensations of floating, and imagine the visual, auditory, olfactory, and tactile details of a pleasant scene of their choosing. The script provided suggestions for transforming pain into sensations of warmth, coolness, or tingling. This script closely followed a standardized self-hypnotic induction script (see supplementary materials) validated in prior research on self-hypnosis during acute medical procedures.22 The mindfulness and hypnotic suggestion scripts were exactly equal in number of words.

Psychoeducation

The psychoeducation condition consisted in a single 15-min session in which a social worker provided empathic responses to the patient and then attempted to increase perception of pain control by reviewing common behavioral pain coping strategies (e.g., stretching, using hot and cold compresses). The psychoeducation condition followed a pain coping education brochure utilized throughout the university hospital.

Study interventions were implemented by clinical social workers, each of whom was trained to deliver all three interventions throughout the study. Training comprised 3 h of instruction in empathic responses, mindfulness, and hypnotic suggestion under the supervision of the first author, a clinician with more than 10 years of experience in providing mind-body interventions for patients with pain in medical settings.

Outcome and Assessments

Self-assessments were administered immediately before and after the intervention, which comprised a 15-min interval. Primary outcomes of pain intensity and unpleasantness were measured with two items rated on a numeric rating scale (0–10)—a widely used and validated approach to measuring clinical pain.23 Participants who reported ≥30% reduction in pain intensity were identified as “responders” based on a validated threshold for “moderate clinical benefit” identified in best practice guidelines for pain research.24 Secondary outcomes were measured via validated single items assessing relaxation,25 anxiety,22 pleasant body sensations,26 and desire for opioids,27 all rated on a numeric rating scale (0–10) to minimize patient confusion. There was no follow-up measure of potential impacts of the brief interventions, because we reasoned that no residual benefit of a single intervention session could be expected multiple hours, days, or weeks later.

Power Calculation

A priori power analysis was conducted in G*Power. An estimated total sample size of 244 was needed to detect an overall between-group effect on baseline-adjusted post-treatment pain (f = 0.20, or of small size) with 80% power, two-sided p < 0.05.28

Statistical Analysis

Hypothesis testing was conducted via SPSS version 23 software (IBM Corp., Armonk, NY) using an analysis of covariance (ANCOVA) strategy29 for primary (i.e., pain intensity and pain unpleasantness) and secondary outcomes (anxiety, relaxation, pleasant body sensations, desire for opioids), adjusted for baseline differences. In accordance with a classical ANCOVA approach for analyzing clinical trial outcomes,29 co-varying of baseline values ensures that comparisons of post-intervention values by treatment group are independent of baseline differences. In ANCOVA models, post-intervention values of outcome variables were regressed on intervention group (mindfulness or suggestion vs. education control) after co-varying pre-intervention values. We used linear mixed models with random intercepts under maximum likelihood estimation for intention-to-treat (ITT) analyses of the entire randomized sample. Because opioids might influence pain outcomes, we also controlled for morphine equivalent daily dose (calculated via the Washington State Agency Medical Directors’ Group opioid dose calculator) in the 24-h period prior to intervention as a covariate in a sensitivity analysis. Because significant between-group differences in gender were observed (see Table 1), we controlled for participant gender as a covariate in a sensitivity analysis. Though this study was not powered to be a comparative effectiveness or non-inferiority trial with respect to the two mind-body interventions (mindfulness vs. hypnotic suggestion), we conducted exploratory post hoc contrasts to test for between-group differences. Multiple comparisons were adjusted using the Bonferroni-Holm method.