Treatment Effect in Physical Therapy: Understanding Treatment Effect and Modifiers in Musculoskeletal Care

Introduction

In the dynamic world of physical therapy, substantiating value hinges on understanding the mechanisms and levers responsible for effective care delivery. Among these, treatment effects and treatment effect modifiers stand out as critical tools for tailoring interventions and enhancing musculoskeletal care. By exploring how individual characteristics influence objective outcomes and quality of care reception, clinicians can refine strategies to achieve both efficiency and efficacy.

This blog explores the growing emphasis on personalized MSK therapy, focusing on the unique factors that shape recovery trajectories. From optimizing treatment plans to improving patient satisfaction, we’ll uncover the evidence-backed methods to elevate the value of physical therapy services. Let’s explore how these levers can drive impactful, patient-centered care.

Chapter 1: Introduction to Treatment Effects in Physical Therapy

In the evolving landscape of physical therapy practice, the concept of precision medicine—providing the right therapy to the right patient at the right time—has gained significant traction. Central to this approach is understanding treatment effect modifiers: the individual characteristics that influence how patients respond to specific interventions.

Physical therapists routinely observe that patients with seemingly similar conditions respond differently to the same intervention. This variability in treatment response highlights the importance of moving beyond a one-size-fits-all approach toward more personalized care strategies. In order to gauge the essential “value” MSK care, we need to identify substance and noise in care provision process. By identifying and understanding the treatment effect modifiers, clinicians can optimize outcomes and enhance the efficiency of their interventions.

This blog post examines recent research on treatment effect modifiers in physical therapy for musculoskeletal pain, with a particular focus on low back pain based on a recent series of articles. We'll explore how various patient characteristics can influence treatment outcomes and discuss the implications for clinical practice. Value Based Care substantiated in evidence needs to appreciate the entire trajectory of clinical encounter and clinical experience. Treatment effect and treatment effect modifiers can help us explain the substance of MSK care delivery, including objective and experiential factors.

Chapter 2: Understanding Types of Treatment Effects

Before diving into specific modifiers, it's important to understand the different ways researchers conceptualize and measure treatment effects:

Average Treatment Effect (ATE)

This represents the average effect of a treatment across the entire eligible population or sample. It's calculated as the difference in expected outcomes between treated and untreated groups, assuming random assignment.

Average Treatment Effect on the Treated (ATT)

This measures the average effect specifically among those who received the treatment, making it useful for understanding the impact on individuals who actively participated in the intervention.

Average Treatment Effect on the Untreated (ATU)

This represents the hypothetical average effect of a treatment on individuals who did not receive it.

Conditional Average Treatment Effect (CATE)

This reflects the average treatment effect within subgroups defined by specific covariates (e.g., age, gender, comorbidities) and is used in heterogeneous treatment effect models to account for variation across different populations.

Local Average Treatment Effect (LATE)

This focuses on individuals whose treatment assignment was influenced by an instrumental variable (e.g., physician identity or day of admission) and applies to cases where compliance with treatment assignment varies.

Person-Centered Treatment Effect (PeT)

This estimates individual-level treatment effects based on observed characteristics and instrumental variables.

In clinical research, treatments are often evaluated using either homogeneous models (assuming all individuals experience the same change due to treatment) or heterogeneous models (allowing for variation in treatment effects across individuals or subgroups). The latter approach is essential for identifying treatment effect modifiers and developing personalized care strategies.

Chapter 3: Treatment Effect Modifiers in Acute Low Back Pain

The TARGET trial provides valuable insights into treatment effect modifiers for acute low back pain, particularly in high-risk patients. This secondary analysis investigated how different patient characteristics influenced the effectiveness of Psychologically Informed Physical Therapy (PIPT) compared to usual care.

Key Modifiers Identified:

Smoking Status

Smokers demonstrated significantly greater improvement in disability scores (measured by the Oswestry Disability Index, ODI) with PIPT compared to usual care. This suggests that smokers, who might typically have poorer outcomes with standard care, may particularly benefit from the more comprehensive PIPT approach.

Pain Medication Use

Patients prescribed three or more pain medications showed notable improvement with PIPT over usual care. This indicates that patients with more complex pain presentations requiring multiple medications might respond better to the multidimensional approach of PIPT.

Factors Without Significant Modifying Effects

Characteristics like age, gender, and ethnicity did not significantly modify treatment outcomes in this population. Socioeconomic Status (SES) and Body Mass Index (BMI) were identified as possible factors but did not show consistent, interpretable effects.

These findings highlight the potential for tailoring interventions based on specific patient characteristics, particularly for high-risk patients with acute low back pain.

Chapter 4: Treatment Effect Modifiers in Persistent Low Back Pain

Extending our understanding to persistent low back pain, Hayden et al. (2019) conducted an individual participant data (IPD) meta-analysis examining treatment effect modifiers in exercise therapy. This comprehensive analysis included 3,514 individuals from 27 randomized controlled trials.

Overall Treatment Effectiveness

The study confirmed that exercise therapy:

• Reduced pain by a clinically important margin compared with no treatment/usual care (Mean Difference [MD] -10.7, 95% CI: -14.1 to -7.4)

• Improved functional limitations by 23% compared with no treatment/usual care (MD -10.2, 95% CI: -13.1 to -7.3)

• Enhanced global recovery significantly compared to no treatment/usual care (Odds Ratio [OR] 3.8, 95% CI: 2.6 to 5.7)

Key Modifiers Identified:

Body Mass Index (BMI)

Patients with lower BMI (normal range) experienced better pain reduction and global recovery outcomes with exercise therapy. This suggests that body weight may influence the effectiveness of exercise interventions, potentially due to biomechanical factors or general exercise capacity.

Occupational Physical Demands

Patients without heavy physical demands at work showed better functional improvement with exercise. This indicates that occupational factors play a role in treatment response and may need to be considered when designing exercise programs.

Medication Use

Individuals who used medication for their low back pain had better pain reduction, functional improvement, and global recovery outcomes with exercise therapy. This suggests a potential synergistic effect between pharmacological and exercise interventions.

Other Potential Modifiers

The study also identified longer duration of chronic low back pain and sick leave within the past 12 months as potential modifiers, though these findings were considered exploratory.

These insights highlight the importance of considering individual patient characteristics when prescribing exercise therapy for persistent low back pain.

Chapter 5: Specific vs. Non-Specific Effects in Physical Therapy

An often-overlooked aspect of treatment effects is the distinction between specific effects (directly attributable to the intervention) and non-specific effects (arising from contextual factors, patient expectations, and therapeutic alliance). Ezzatvar et al. (2024) conducted a meta-analysis to quantify the proportion of physiotherapy treatment effects not attributable to specific effects for musculoskeletal pain.

Key Findings on Non-Specific Effects:

Pain Outcomes

• Mobilization had the highest PCE for immediate pain relief (87%), indicating that most of its effects may be contextual

• Soft tissue techniques (81%) and dry needling (75%) also showed high proportions of non-specific effects

• Exercise therapy had the lowest PCE (46%), suggesting a higher proportion of its effects were specific to the intervention

Disability Outcomes

• Taping had the largest PCE for disability improvement (64%)

• Mobilization (47%) and manipulation (40%) showed moderate proportions of non-specific effects

Influence of Placebo Type

• Nonmanual placebos (e.g., detuned devices) had a higher PCE (83%) compared to manual placebos (70%), suggesting stronger contextual effects in technologically advanced interventions

These findings highlight the substantial role of non-specific effects in physiotherapy outcomes for musculoskeletal pain. Understanding and ethically leveraging these effects could enhance therapeutic benefits.

Chapter 6: Physical Therapy for Persistent Post-Surgical Pain

Extending our exploration to another important clinical area, Robinson et al. (2019) systematically reviewed the effectiveness of physiotherapy interventions for persistent post-surgical pain (PPSP). This review evaluated outcomes including pain, quality of life, physical function, and depression.

Key Findings:

Pain Reduction

All eight studies reported positive impacts of physiotherapy interventions on pain, with four studies demonstrating statistically significant improvements (p<0.05).

Quality of Life (QoL)

Two studies reported significant improvements in QoL using WOMAC and SF-36 questionnaires.

Physical Function

Improvements in physical function were observed in two studies, with statistically significant results in the 6-Minute Walk Test (6MWT) and Timed Up and Go (TUG) tests.

Depression

Two studies measured depression symptoms, with one reporting statistically significant reductions.

The review noted that physiotherapy interventions often included a package of care addressing multifactorial components of PPSP, suggesting that comprehensive approaches may be more effective than isolated techniques.

While the evidence was promising, methodological limitations and heterogeneity in interventions and outcome measures necessitate cautious interpretation and further research.

Chapter 7: Clinical Implications for Physical Therapists

The research discussed in this blog post offers several important implications for clinical practice:

1. Embracing Patient-Centered Assessment

Thorough assessment should include potential treatment effect modifiers such as:

• Smoking status and pain medication use for acute low back pain

• BMI, occupational demands, and medication use for persistent low back pain

• Psychosocial factors that might influence both specific and non-specific treatment effects

2. Tailoring Interventions Based on Modifiers

• For smokers or patients on multiple pain medications with acute LBP, consider psychologically informed physical therapy approaches

• For patients with persistent LBP, exercise prescription may be more effective for those with normal BMI, less physically demanding occupations, and those using pain medications

• Consider the substantial contribution of non-specific effects in manual therapy techniques and leverage these ethically to enhance outcomes

3. Balancing Specific and Non-Specific Effects

• Recognize that interventions like mobilization and soft tissue techniques derive substantial benefits from contextual factors

• Exercise therapy appears to have more specific effects, making it particularly important to prescribe appropriate exercises

• The therapeutic relationship and communication style may significantly influence outcomes, particularly for interventions with high non-specific effect proportions

4. Comprehensive Approaches for Complex Pain

• For conditions like persistent post-surgical pain, multimodal approaches addressing various aspects of pain experience may be more effective than isolated techniques

• Consider the potential impacts on quality of life, physical function, and psychological well-being beyond pain reduction

Chapter 8: Future Directions and Research Needs

While the studies reviewed provide valuable insights, several gaps remain in our understanding of treatment effect modifiers in physical therapy:

1. Methodological Improvements

Future research would benefit from:

• Larger sample sizes to enable robust subgroup analyses

• Consistent measurement and reporting of potential modifiers

• More diverse study populations to enhance generalizability

2. Expanding the Range of Modifiers

Research should explore additional potential modifiers including:

• Genetic factors

• Psychological traits beyond those currently studied

• Social determinants of health

• Comorbid conditions

3. Implementation Science

We need more research on how to effectively:

• Integrate knowledge of treatment effect modifiers into clinical decision-making

• Develop and validate clinical prediction rules

• Implement personalized care approaches in various practice settings

4. Objective Outcome Measures

Future studies should incorporate more objective measures alongside patient-reported outcomes to provide a more comprehensive understanding of treatment effects.

Conclusion

As always, we need to separate the dichotomy of “Physical Therapy” as a service, and “Physical Therapy” as a model of care delivery. Treatment effects, including direct and indirect effects, can help us gauge and understand the need for substantiative care delivery models, that better explain the “dosing” and quality of care provision through the length of clinical encounter, that often goes beyond the traditional course of care. The journey toward personalized physical therapy requires understanding not just what works, but for whom and under what circumstances. The research on treatment effect modifiers provides a foundation for moving beyond one-size-fits-all approaches toward more targeted, efficient, and effective care.

Clinicians and consumers need to be aware of the complexity of systems impacting delivery and reception of care services. Direct and indirect levers impact qualitative and objective clinical outcomes. By considering factors such as smoking status, medication use, BMI, and occupational demands—as well as the balance between specific and non-specific effects—physical therapists can make more informed decisions about intervention selection and delivery.

As our understanding of treatment effect modifiers continues to evolve, so too will our ability to optimize outcomes for individuals with musculoskeletal pain. The future of physical therapy lies in this personalized approach, where interventions are tailored to the unique characteristics of each patient we serve.

References

Ezzatvar, Y., Dueñas, L., Balasch-Bernat, M., Lluch-Girbés, E., & Rossettini, G. (2024). Which portion of physiotherapy treatments' effect is not attributable to the specific effects in people with musculoskeletal pain? A meta-analysis of randomized placebo-controlled trials. Journal of Orthopaedic & Sports Physical Therapy, 54(6), 391–399. https://doi.org/10.2519/jospt.2024.12126

Hayden, J. A., Wilson, M. N., Stewart, S., Cartwright, J. L., Smith, A. O., Riley, R. D., van Tulder, M., Bendix, T., Cecchi, F., Costa, L. O. P., et al. (2019). Exercise treatment effect modifiers in persistent low back pain: An individual participant data meta-analysis of 3514 participants from 27 randomized controlled trials. British Journal of Sports Medicine. https://doi.org/10.1136/bjsports-2019-101205

Robinson, A., McIntosh, J., Peberdy, H., Wishart, D., Brown, G., Pope, H., & Kumar, S. (2019). The effectiveness of physiotherapy interventions on pain and quality of life in adults with persistent post-surgical pain compared to usual care: A systematic review. PLOS ONE, 14(12), e0226227. https://doi.org/10.1371/journal.pone.0226227

TARGET trial secondary analysis: Treatment effect modifiers for individuals with acute low back pain. (n.d.). Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC6794006/