Interdisciplinary Outpatient Multimodal Pain Treatment After Non-Confirmation of Surgical Indication for Persistent Spinal Pain: Real-World Outcomes in 9,217 Patients (RESPONSE Study)

20/03/2026
20/03/2026
EU PAS number:
EUPAS1000000952
Study
Finalised
Study type

Study topic

Disease /health condition

Study topic, other

persistant spinal pain

Study type

Non-interventional study

Scope of the study

Effectiveness study (incl. comparative)
Evaluation of patient-reported outcomes

Data collection methods

Secondary use of data
Non-interventional study

Non-interventional study design

Cohort
Study drug and medical condition

Medical condition to be studied

Spinal pain
Population studied

Short description of the study population

The study population consists of adult patients with persistent spinal pain who were referred for an interdisciplinary second-opinion assessment prior to planned spinal surgery within a structured healthcare program in Germany.

Patients entered the second-opinion process after spinal surgery had been recommended or considered during routine clinical care. In contrast to conventional mono-disciplinary second-opinion procedures, the evaluation within this program is performed by an interdisciplinary team including a pain medicine specialist with formal qualification in pain medicine, a pain psychologist, and a pain physiotherapist. The purpose of this assessment is to evaluate the patient’s condition within a biopsychosocial framework that considers structural findings, functional impairment, psychological factors, and the degree of pain chronification.

Based on this interdisciplinary evaluation, a treatment recommendation is formulated and discussed with the patient in a structured shared decision-making process. Possible outcomes of the second-opinion assessment include confirmation of the surgical indication, recommendation of optimized conservative treatment within routine care, or referral to an intensive outpatient interdisciplinary multimodal pain treatment program.
The present study focuses exclusively on patients in whom the originally proposed spinal surgery was not confirmed during interdisciplinary evaluation and for whom the interdisciplinary team recommended participation in the intensive outpatient interdisciplinary multimodal pain treatment program. This recommendation was typically made in patients presenting with substantial pain-related disability, advanced pain chronification, or complex biopsychosocial factors indicating the need for structured interdisciplinary treatment.
Between January 2014 and December 2025, a total of 13,316 patients underwent interdisciplinary second-opinion assessment within the program. Surgical indication was confirmed only in a small proportion of cases, while the majority of patients were referred to conservative treatment pathways, including the intensive outpatient interdisciplinary multimodal pain treatment program.
The study cohort consists of 9,217 consecutive patients who participated in and completed the three-week outpatient treatment program and for whom both baseline and post-treatment outcome data were available. Recruitment was consecutive within the participating centers during the study period, reflecting routine clinical care without additional study-related selection procedures.

Inclusion criteria
Patients were eligible for inclusion in the present analysis if they met the following criteria:
referral for interdisciplinary second-opinion assessment prior to planned spinal surgery
non-confirmation of the surgical indication during interdisciplinary evaluation
recommendation for participation in the intensive outpatient interdisciplinary multimodal pain treatment program
completion of the three-week outpatient treatment program
availability of both baseline and post-treatment outcome data.

Exclusion criteria
Patients were not included in the analysis if the originally proposed surgical intervention was confirmed during the second-opinion process or if the interdisciplinary team recommended alternative treatment pathways that did not include participation in the outpatient multimodal program. Patients with incomplete baseline or post-treatment documentation were also excluded from the analytic dataset.

Clinical characteristics of the study population
The study population represents a clinically complex group of patients with persistent spinal pain and substantial disease burden. Many patients had experienced long-standing pain conditions and had previously undergone extensive diagnostic and therapeutic interventions. A considerable proportion of patients had also undergone prior spinal surgery and therefore formally fulfilled the criteria of persistent spinal pain syndrome type 2 (PSPS-2).
The severity of pain chronification in the study population was assessed using the Chronic Pain Grading Scale (CPGS). A large proportion of patients belonged to the higher chronification grades, reflecting the substantial functional impairment and multidimensional burden characteristic of this patient population.

Overall, the cohort represents a real-world population of patients with persistent spinal pain who had previously been considered for spinal surgery but were subsequently referred to interdisciplinary multimodal pain treatment following structured interdisciplinary evaluation.

Age groups

  • Adult and elderly population (≥18 years)
    • Adults (18 to < 65 years)
      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)
      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)

Estimated number of subjects

9217
Study design details

Study design

Retrospective real-world cohort study analyzing routine clinical data from patients with persistent spinal pain who entered a structured interdisciplinary outpatient multimodal pain treatment program after non-confirmation of a planned spinal surgery during interdisciplinary 2nd-opinion assessment.

Main study objective

The main objective of this study is to evaluate real-world clinical outcomes associated with intensive interdisciplinary outpatient multimodal pain treatment in patients with persistent spinal pain who were initially referred for planned spinal surgery but in whom surgical indication was not confirmed following structured interdisciplinary second-opinion assessment.
Persistent spinal pain represents a major cause of long-term disability and healthcare utilization. In routine care, treatment decisions for patients with chronic spinal pain are often strongly influenced by structural imaging findings and mono-disciplinary clinical evaluation. However, chronic spinal pain is increasingly recognized as a complex biopsychosocial condition in which structural pathology alone often does not sufficiently explain pain intensity, functional impairment, or patient disability. As a result, surgical interventions may not always represent the most appropriate therapeutic option, particularly in patients with advanced pain chronification or significant psychosocial burden.
To address this challenge, a structured interdisciplinary second-opinion model has been implemented within a specialized healthcare program in Germany. This model differs from conventional second-opinion procedures by integrating expertise from multiple disciplines, including pain medicine, pain psychology, and physiotherapy. The purpose of this interdisciplinary evaluation is to assess patients using a comprehensive biopsychosocial framework that considers structural findings, functional limitations, psychological factors, prior treatment history, and the degree of pain chronification.
Patients in whom the originally proposed spinal surgery is not confirmed may be referred to alternative treatment pathways, including an intensive interdisciplinary outpatient multimodal pain treatment program. This program is designed to address the multidimensional nature of chronic pain through coordinated interventions combining medical management, physiotherapy, psychological treatment, patient education, and self-management strategies.
Although interdisciplinary multimodal pain therapy has been shown to be effective in various clinical settings, much of the existing evidence originates from inpatient treatment programs. Data on large-scale outpatient interdisciplinary programs implemented under routine clinical conditions remain comparatively limited. Evaluating the effectiveness of such programs in real-world healthcare settings is therefore essential for informing clinical practice and healthcare policy.
The primary objective of the present study is therefore to assess short-term changes in pain-related disability following completion of a structured three-week intensive outpatient interdisciplinary multimodal pain treatment program. Pain-related disability is measured using the modified Pain Disability Index (mPDI), a validated instrument assessing the impact of pain on multiple domains of daily life.
Secondary objectives include evaluating treatment-associated changes across a range of additional biopsychosocial outcome domains that reflect the multidimensional nature of chronic pain. These outcomes include pain intensity, functional capacity, psychological distress, health-related quality of life, fear-avoidance beliefs, pain-related self-efficacy, and habitual well-being.
Another key objective of the study is to examine whether patients with different levels of baseline pain severity and chronification derive comparable benefit from outpatient interdisciplinary multimodal treatment. To address this question, outcomes are analyzed across predefined severity strata based on the Chronic Pain Grading Scale (CPGS), which categorizes patients according to pain intensity and pain-related disability.
Particular attention is given to patients with high levels of pain chronification and functional impairment, corresponding to the highest CPGS severity grade. These patients are often considered difficult to treat in outpatient settings and are frequently assumed to require more intensive inpatient care. Evaluating treatment outcomes in this subgroup therefore provides important information regarding the potential role of structured outpatient programs within stepped-care models of chronic pain management.
The study further aims to characterize the clinical complexity of patients entering the outpatient multimodal treatment program. This includes describing prior treatment exposure, including pharmacological therapies, interventional pain procedures, and previous spinal surgery. A substantial proportion of patients in the cohort have undergone prior spinal surgery and therefore fulfill the criteria for persistent spinal pain syndrome type 2 (PSPS-2), representing a particularly challenging patient population.
Finally, the study seeks to examine whether treatment-associated improvements occur consistently across participating treatment centers and patient subgroups. Multivariable statistical analyses are therefore used to evaluate whether treatment outcomes remain stable after adjustment for demographic characteristics and treatment center effects.
Overall, the study aims to generate robust real-world evidence on the clinical outcomes associated with interdisciplinary outpatient multimodal pain treatment following non-confirmation of surgical indication for persistent spinal pain. By evaluating outcomes in a large consecutive cohort of patients treated under routine clinical conditions, the study contributes to a better understanding of the potential role of structured outpatient multimodal programs as part of integrated care pathways for patients with chronic spinal pain.

Setting

The source population consists of adult patients with persistent spinal pain who were referred for interdisciplinary second-opinion assessment prior to planned spinal surgery within a structured healthcare program in Germany. The program is implemented in a nationwide network of specialized pain treatment centers providing interdisciplinary evaluation including pain medicine, pain psychology, and physiotherapy.
Patients entered the second-opinion process after spinal surgery had been recommended or considered during routine clinical care. Within the program, patients underwent a structured interdisciplinary assessment designed to evaluate the appropriateness of surgical treatment within a biopsychosocial framework that considers structural findings, functional impairment, psychological factors, and the degree of pain chronification.
The study period covers January 2014 to December 2025. During this time, 13,316 patients underwent interdisciplinary second-opinion evaluation within participating centers.
The study cohort consists of 9,217 consecutive patients in whom the originally proposed surgical intervention was not confirmed during interdisciplinary evaluation and who were subsequently referred to a structured three-week interdisciplinary outpatient multimodal pain treatment program. Inclusion required participation in and completion of the treatment program as well as availability of both baseline and post-treatment outcome data from routine clinical documentation.
Patients in whom the surgical indication was confirmed or in whom alternative treatment pathways were recommended were not included in the present analysis.
The study therefore evaluates outcomes within a single structured treatment pathway following non-confirmation of surgical indication. No separate treatment arms or comparators are defined. For analytical purposes, patients are stratified according to baseline pain severity and chronification using the Chronic Pain Grading Scale (CPGS).

Comparators

None

Outcomes

The primary outcome of the study is the short-term change in pain-related disability following completion of a structured three-week interdisciplinary outpatient multimodal pain treatment program. Pain-related disability is measured using the modified Pain Disability Index (mPDI), a validated patient-reported outcome instrument assessing the impact of pain on multiple domains of daily functioning. The primary endpoint is defined as the absolute change in mPDI score between baseline assessment prior to treatment initiation and the post-treatment assessment at end of the 3-week intervention.
Secondary outcomes include changes in several additional patient-reported outcome measures reflecting key domains of the biopsychosocial model of chronic pain. These outcomes include pain intensity assessed using visual analogue scale (VAS) measures for lowest, average, and highest pain intensity over the previous 24 hours; functional capacity measured with the Hannover Functional Ability Questionnaire (HFAQ); and health-related quality of life assessed using the physical and mental component scores of the VR-12 health survey.
Psychological outcomes include levels of psychological distress measured with the Depression Anxiety Stress Scales (DASS-21), fear-avoidance beliefs assessed with the Fear-Avoidance Beliefs Questionnaire (FABQ), and pain-related self-efficacy assessed using the Pain Self-Efficacy Questionnaire (PSEQ). General well-being is assessed using the Marburg Questionnaire on Habitual Health Findings (MQHHF).
Responder analyses are additionally conducted for the primary outcome using predefined thresholds for clinically meaningful improvement in pain-related disability. All outcomes are assessed at baseline prior to treatment initiation and at completion of the three-week outpatient treatment program.
Outcomes are evaluated across predefined severity strata based on the Chronic Pain Grading Scale (CPGS), allowing subgroup assessments of treatment changes.

Data analysis plan

All analyses will be conducted using anonymized routine care data derived from standardized clinical documentation. Descriptive statistics will be used to characterize the study population at baseline. Continuous variables will be summarized using means and standard deviations, while categorical variables will be reported as frequencies and percentages.
The primary analysis will evaluate within-patient changes in pain-related disability measured by the modified Pain Disability Index (mPDI) between baseline assessment prior to treatment initiation and the post-treatment assessment at completion of the three-week interdisciplinary outpatient multimodal pain treatment program. Changes in continuous outcomes will be assessed using paired statistical tests.
Standardized effect sizes for within-group changes will be calculated using Cohen’s d for dependent samples, defined as the mean change divided by the standard deviation of the individual change scores.
Secondary analyses will evaluate treatment-associated changes across additional patient-reported outcomes reflecting multiple domains of chronic pain, including pain intensity, functional capacity, psychological distress, fear-avoidance beliefs, health-related quality of life, pain self-efficacy, and habitual well-being.
To examine potential differences in treatment effects across baseline severity levels, analyses will be stratified according to Chronic Pain Grading Scale (CPGS) categories. Between-group comparisons will be conducted using analysis of covariance (ANCOVA) adjusting for baseline values.
Multivariate analyses of covariance (MANCOVA) will be applied to examine change patterns across multiple outcome domains simultaneously while adjusting for potential confounders including age, sex, and treatment center.
All analyses are exploratory and aim to describe treatment-associated outcome changes under real-world clinical conditions.

Summary results

During the study period, 13,316 patients with persistent spinal pain underwent interdisciplinary second-opinion assessment prior to planned spinal surgery. Surgical indication was confirmed in only a small proportion of cases. Overall, 9,217 patients in whom surgery was not confirmed entered and completed the structured three-week interdisciplinary outpatient multimodal pain treatment program and were included in the analysis.
The study population represented a clinically complex group with substantial disease burden. Nearly half of the cohort (45.7%) was classified as Chronic Pain Grading Scale (CPGS) grade IV, indicating severe pain-related disability. A considerable proportion of patients had undergone prior spinal surgery and therefore fulfilled the criteria of persistent spinal pain syndrome type 2 (PSPS-2).
Significant improvements were observed across all evaluated outcome domains after completion of the treatment program. Pain-related disability measured by the modified Pain Disability Index (mPDI) decreased substantially across all baseline severity strata, with the largest absolute improvements observed in patients with the highest baseline disability.
Responder analyses showed clinically meaningful improvement in a large proportion of patients; 74.1% of CPGS IV patients achieved an absolute reduction of at least 20 points in mPDI. Improvements were also observed for pain intensity, functional capacity, psychological distress, quality of life, and pain self-efficacy.