Table 1.

Primary and secondary outcome measures

	Justification
Primary outcome measures (analgesic effect)
Change in pain intensity measured by the VAS	The VAS is a continuous variable represented on a 10 cm line, ranging from ‘no pain’ (0 cm) to ‘worst imaginable pain’ (10 cm). We will assess the changes between the baseline and end-of-treatment scores. Primarily, we will consider as responders those patients with a ≥30% reduction in the ‘maximum pain intensity in the last 24 hours’ at any given time during the study compared with the baseline score (study start visit) for at least three consecutive days.
PIDs from baseline during the 28 days of treatment	This outcome measure will be used to assess pain intensity evolution during the 28 days of treatment and to obtain the SPID (area under the time-analgesic effect curve).
Scores on the McGill Multidimensional Pain Questionnaire	The scores range from 0 (no pain) to 78 (severe pain). We will assess the changes between the baseline and end-of-treatment scores.
Secondary outcome measures
Other analgesic effect measures
Change in pain intensity measured by the VAS	Other definitions of responder will be considered when assessing pain intensity with the VAS, in order to allow capturing different nuances in the response: Alternative responder 1: ≥50% reduction in the ‘maximum pain intensity in the last 24 hours’ at any given time during the study compared with the baseline score (study start visit) for at least three consecutive days. Alternative responder 2: ≥30% reduction in the ‘current pain’ at any given time during the study compared with the baseline score (study start visit) for at least three consecutive days. Alternative responder 3: ≥50% reduction in the ‘current pain’ at any given time during the study compared with the baseline score (study start visit) for at least three consecutive days. Alternative responder 4: ≥30% reduction in the ‘maximum pain intensity in the last 24 hours’ and in the ‘current pain’ at any given time during the study compared with the baseline score (study start visit) for at least three consecutive days. Alternative responder 5: ≥50% reduction in the ‘maximum pain intensity in the last 24 hours’ and in the ‘current pain’ at any given time during the study compared with the baseline score (study start visit) for at least three consecutive days.
Requirement of rescue analgesia	As an alternative way of measuring pain intensity. Therefore, we will consider another definition of responder: Alternative responder 6: patients who do not require rescue analgesia
Anxiety, depression, mood state and global improvement
Change of status according to the HADS scores.	The HADS is composed of two subscales, one for depression and the other for anxiety. Each subscale consists of seven items; each item score ranges from 0 (best result possible) to 3 (worst result possible). A final subscale score is achieved by summing the items scores. Final subscale scores ranging from 0 to 7 denote normal levels of anxiety/depression; scores ranging from 8 to 10 denote borderline cases; and scores ranging from 11 to 21 denote abnormal cases.
Mean TMD scores (measured by the POMS)	The POMS questionnaire assesses six mood subscales: tension anxiety, depression, anger hostility, vigour, fatigue and confusion. High vigour scores reflect a good mood or emotion, and low scores in the other subscales reflect a good mood or emotion. The TMD score is obtained by adding the five negative subscale scores (tension anxiety, depression, anger-hostility, vigour, fatigue and confusion) and subtracting the vigour score. Higher TMD scores indicate greater degrees of mood disturbance.
Mean PGIC scores at the end-of-treatment visit	The PGIC is a self-reported 7-point scale depicting a patient’s rating of overall improvement. Patients rate their change as ‘very much improved’, ‘much improved’, ‘minimally improved’, ‘no change’, ‘minimally worse’, ‘much worse’ or ‘very much worse’.
Quality of life
Mean change in the SF-36 scores	The SF-36 consists of 36 questions meant to reflect 8 health domains, including physical functioning, physical role, pain, general health, vitality, social function, emotional role and mental health. Scores range from 0 (maximum disability) to 100 (no disability).
Change in the EQ-5D-5L scores	The EQ-5D-5L comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has five levels: no problems (1), slight problems (2), moderate problems (3), severe problems (4) and extreme problems (5). The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a one-digit no that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit no that describes the patient’s health state.
Safety
No of AEs by treatment arm	To assess the overall no of AEs in each group.
No of side effects derived from opioid use	These will be assessed by the UKU Side Effect Rating Scale, a comprehensive rating scale that includes 48 individual side effects that can be grouped into the four main dimensions of psychic, neurological, autonomic and other side effects.
No of AEs related to the treatments under study (musicbooks or audiobooks listening)	No of adverse events considered as TEAEs.
Mean change in the ORT score	The ORT is a brief, self-report screening tool to assess the risk for opioid abuse among individuals prescribed opioids for treatment of chronic pain. Total scores of ≤3 indicate low risk for future opioid abuse; 4–7 indicate moderate risk and a score of ≥8 indicates a high risk.
Mean change in the SOAPP-R questionnaire score	The SOAPP-R is a 24-item questionnaire created to help determine how much monitoring a patient on long-term opioid therapy might require. Questions are scored from 0 (best result) to 4 (worst result). A total score of ≥18 indicates that monitoring is required.

AE, adverse event; EQ-5D-5L, EuroQoL-5 Dimensions-5 Levels; HADS, Hospital Anxiety and Depression Scale; ORT, Opioid Risk Tool; PGIC, Patient Global Impression of Change; PID, pain intensity differences; POMS, Profile of Mood States; SF-36, Short-Form 36 Health Survey; SOAPP-R, Revised Screener and Opioid Assessment for Patients with Pain; SPID, sum of PID; TEAE, treatment-emergent adverse event; TMD, total mood disturbance; UKU, Udvalg für Kliniske Undersøgelse; VAS, Visual Analogue Scale.