[ literature review ]

YASMIN EZZATVAR, PT, PhD1 • LIRIOS DUEÑAS, PT, PhD2 • MERCÈ BALASCH-BERNAT, PT, PhD2
ENRIQUE LLUCH-GIRBÉS, PT, PhD2a • GIACOMO ROSSETTINI, PT, PhD3,4a

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
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P
U OBJECTIVE: We aimed to quantify the proportion therapy interventions included soft tissue tech- hysical therapists use dif­
Copyright © 2024 Journal of Orthopaedic & Sports Physical Therapy®. All rights reserved.

not attributable to the specific effects (PCE) of physi- niques, mobilization, manipulation, taping, exer- ferent interventions when
cal therapy interventions for musculoskeletal pain. cise therapy, and dry needling. Placebo interven-
treating musculoskeletal
U DESIGN: Intervention systematic review with tions included manual, nonmanual interventions,
pain disorders.44 Although
or both. The proportion not attributable to the
meta-analysis.
specific effects of mobilization accounted for 88% compelling evidence exists about the
U LITERATURE SEARCH: We searched Ovid, of the immediate overall treatment effect for pain efficacy and cost-effectiveness of inter-
MEDLINE, EMBASE, CINAHL, Scopus, PEDro, Cochrane intensity (PCE = 0.88, 95% confidence interval ventions such as joint mobilizations/ma-
Controlled Trials Registry, and SPORTDiscus [CI]: 0.57, 1.20). In exercise therapy, this proportion
databases from inception to April 2023. nipulations, soft tissue techniques, neural
accounted for 46% of the overall treatment effect
U STUDY SELECTION CRITERIA: Randomized for pain intensity (PCE = 0.46, 95% CI: 0.41, 0.52). mobilizations, exercise therapy, taping
The PCE in manipulation excelled in short-term and dry needling,2,7,11,15,25,28,32,39 and high-
Journal of Orthopaedic & Sports Physical Therapy®

placebo-controlled trials evaluating the effect of physi-

cal therapy interventions on musculoskeletal pain. pain relief (PCE = 0.81, 95% CI: 0.62, 1.01) and quality clinical practice guidelines recom-
U DATA SYNTHESIS: Risk of bias was evaluated
in mobilization in long-term effects (PCE = 0.86, mend them for managing musculoskeletal
95% CI: 0.76, 0.96). In taping, the PCE accounted
using the Cochrane risk-of-bias tool for randomized pain,24 the mechanisms of action are not
for 64% of disability improvement (PCE = 0.64,
trials (RoB 2). The proportion of physical therapy well understood.3,5 Understanding how
95% CI: 0.48, 0.80).
interventions effect that was not explained by the physical therapy interventions work un-
specific effect of the intervention was calculated, U CONCLUSION: The outcomes of physical
therapy interventions for musculoskeletal pain were
derscores the biological plausibility of
using the proportion not attributable to the specific
effects (PCE) metric, and a quantitative summary significantly influenced by factors not attributable to physical therapy practice and provides
of the data from the studies was conducted us- the specific effects of the interventions. Boosting these evidence of its therapeutic value.4,17
ing the random-effects inverse-variance model factors consciously to enhance therapeutic outcomes The outcome of treatment (total or over-
(Hartung-Knapp-Sidik-Jonkman method). represents an ethical opportunity that could benefit pa- all treatment effect) is the result of specific
U RESULTS: Sixty-eight studies were included in
tients. J Orthop Sports Phys Ther 2024;54(6):391-399.
effects derived from the intervention itself,
Epub 11 April 2024. doi:10.2519/jospt.2024.12126
the systematic review (participants: n = 5238), nonspecific effects, including the Haw-
and 54 placebo-controlled trials informed our U KEY WORDS: contextual effects,
thorne effect, natural history, regression to
meta-analysis (participants: n = 3793). Physical musculoskeletal pain, physiotherapy, placebo
the mean, and contextual effects.3,4,6,8 The

1
Department of Nursing, University of Valencia, Valencia, Spain. 2Physiotherapy in Motion, Multi-Specialty Research Group (PTinMOTION), Department of Physiotherapy, Faculty
of Physiotherapy, University of Valencia, Valencia, Spain. 3School of Physiotherapy, University of Verona, Verona, Italy. 4Department of Physiotherapy, Faculty of Sport Sciences,
Universidad Europea de Madrid, Villaviciosa de Odón, Spain. aThese two authors contributed equally to this work. ORCID: Ezzatvar, 0000-0002-9691-5998; Dueñas, 0000-
0001-8592-1738; Rossettini, 0000-0002-1623-7681. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
One author leads education programs on placebo, nocebo effects and contextual factors in health care to under- and postgraduate students along with private continuing
professional development (CPD) courses. Research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict
of interest. Giacomo Rossettini leads education programs on placebo, nocebo effects, and contextual factors in healthcare to under- and post-graduate students along with
private CPD courses. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a
potential conflict of interest. Ethical approval was not required for this meta-analysis as it involved the synthesis of existing data from previously conducted studies (PROSPERO
registration number CRD42022380322). Address correspondence to Lirios Dueñas, Department of Physiotherapy, Faculty of Physiotherapy, University of Valencia, 46010
Valencia, Spain. E-mail: [email protected] t Copyright ©2024 JOSPT®, Inc

journal of orthopaedic & sports physical therapy | volume 54 | number 6 | june 2024 | 391
 [ literature review ]
effects that are not derived from the spe- proportion by type of intervention (eg, vasive physical therapy techniques such as
cific intervention itself are often termed manipulation, mobilization, taping, ex- dry needling);44 (3) comparator: a placebo-
placebo effects in clinical trials and placebo ercise therapy, dry needling) and type of controlled group; (4) outcomes analyzed:
responses in clinical practice.18,46 Contex- placebo (eg, manual versus nonmanual). pain intensity, disability; and (5) study de-
tual effects are embedded within a clinical sign: randomized placebo-controlled trials.
encounter (eg, physical therapist’s and pa- METHODS Studies in which the treatment of the
tient’s features, patient-physical therapist experimental group included nutritional

T
relationship, characteristics of the treat- he Preferred Reporting Items supplementation, drugs, surgery, electro-
ment and the healthcare setting),10,13 and for Systematic Reviews and Meta- physical agents (ie, laser therapy, electro-
drive positive or negative therapeutic outco Analyses (PRISMA) guidelines and analgesia, microwaves), psychologically
mes.29,30,38 In research, the specific treat- recommendations27 guided the conduct informed practice, a combination of vari-
ment effect can be isolated by comparing and reporting of our systematic review. ous physical therapy techniques, educa-
the average therapeutic outcomes of a treat- We prospectively registered the review tion, or self-management were excluded.
ment group versus a placebo group within in the International Prospective Register Studies whose participants experienced
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a randomized controlled trial (RCT).8 The of Systematic Reviews (PROSPERO; reg- pain derived from neurological disorders,
RCT design allows for controlling both the istration number CRD42022380322). cancer-related pain, visceral pain, or post-
nonspecific effects and contextual effects of Deviations from the protocol are report- surgical pain were also excluded. Both
an intervention.8 The proportion not attrib- ed in SUPPLEMENTAL FILE 1. As a systematic authors assessed the full-text articles for
utable to the specific effects (PCE) is a new review with meta-analysis, this study did eligibility. Any disagreement was resolved
Copyright © 2024 Journal of Orthopaedic & Sports Physical Therapy®. All rights reserved.

metric designed to capture the therapeutic not directly involve patients in the re- by consensus with a third author (ELL).
outcomes that are not attributable to the search process. Interrater agreement was estimated by
specific effects on an intervention.40 The using Cohen’s kappa statistic (κ), consid-
PCE ranges from 0 to 1, and a larger value Data Sources and Search Strategy ering that κ = 0.01-0.20; κ = 0.21-0.40;
indicates a smaller specific effect of an The search was conducted by two authors κ = 0.41-0.60; κ = 0.61-0.80; κ = 0.81-1.00
intervention.46 Understanding how much (YE and LD), who independently searched indicate a slight, fair, moderate, substan-
nonspecific effects and contextual effects af- in Ovid, MEDLINE, EMBASE, CINAHL, tial and almost perfect level of agreement
fect outcomes helps clinicians and patients Scopus, Physiotherapy Evidence Database among reviewers, respectively.23
make informed treatment decisions.42,45 (PEDro), Cochrane Controlled Trials Reg-
Journal of Orthopaedic & Sports Physical Therapy®

The PCE of general medicine18,40 and istry, and SPORTDiscus databases for ran- Data Extraction
surgery in pain-related conditions22 are domized placebo-controlled trials focused Two authors independently extracted the
generally large. In particular, the overall on evaluating the effect of physical thera- following information from each included
proportion not attributable to the specific py interventions on musculoskeletal pain trial: (1) trial characteristics (first author’s
effects of general medicine interventions is published from inception to April 2023. name, publication year, location, and
high (PCE = 65%), with higher values ob- Only studies written in Spanish, Italian, sample size); (2) demographics (sex, age,
served in semi-objective and objective out- or English languages and published in condition and the number of participants
comes (PCE = 78 and 94%, respectively) peer-reviewed journals were considered. of each group); (3) main outcomes and
than in subjective outcomes (PCE = 50%).40 In addition, the reference lists of the se- method of assessment; (4) intervention,
More than half of the overall treatment ef- lected articles were manually examined placebo and/or control group characteris-
fect observed in musculoskeletal pain con- to retrieve additional potential eligible tics (placebo and intervention type, session
ditions such as knee osteoarthritis,9,46 neck studies. The full search strategy for each duration, sessions per week, intervention
pain,21 low back pain,34,41 and fibromyalgia43 database is reported in SUPPLEMENTAL FILE 2. duration or type of control); and (5) statis-
may be due to factors not related to the in- tical analysis plus outcome of interest and
tended targets of treatment. It is time to Study Selection main results.
disentangle the proportion not attribut- To be included in the meta-analysis, stud- To categorize the effects of the place-
able to the specific effects of interventions ies needed to meet the following PICOS bo and treatment groups, three distinct
in musculoskeletal rehabilitation practice. criteria: (1) participants: minimum age time points were selected: immediate
We aimed to quantify the magnitude of 18 years presenting with musculoskel- effects (immediately after the interven-
of the proportion not attributable to the etal pain conditions (ie, pain that affects tion), short-term effects (between 1 day
specific effects of interventions commonly bones, muscles, ligaments, tendons, and/ and 30 days after the intervention), and
used by physical therapists when manag- or nerves);14,36 (2) intervention: physical long-term effects (beyond 1 month after
ing musculoskeletal pain. Our secondary therapy treatment (ie, manual therapy, the intervention). When relevant infor-
aim was to study the variability of this therapeutic exercise therapy, taping or in- mation from the studies was missing, it

392 | june 2024 | volume 54 | number 6 | journal of orthopaedic & sports physical therapy
 was requested from the corresponding for the analysis and transformed back for of detuned devices like ultrasound, mi-
authors via e-mail. reporting. Its 95% CI was calculated us- crowave, or laser.
ing the Delta method, which allowed us Heterogeneity across RCTs was calcu-
Risk of Bias to calculate the standard error estimator lated using the inconsistency index (I2),
Two authors (LD and YE) independently of the log(PCE).35 considering I2 values of 25%, 50%, and
assessed the risk of bias in eligible stud- Trials were excluded from the analy- 75% as low, moderate, and high variabil-
ies using version 2 of the Cochrane risk- ses if they met any of the following con- ity values due to between-study hetero-
of-bias tool for randomized trials (RoB ditions: (1) the intervention group and geneity, respectively. Publication bias was
2).37 For each RCT and every domain, the the placebo group had a different posi- assessed using doi plots and Luis Furuya–
judgments were “low risk of bias”, “some tive or negative direction of change; (2) Kanamori (LFK) index.16
concerns”, or “high risk of bias”. Any dis- studies in which the intervention elicited Sensitivity analysis was conducted to
crepancies in quality ratings were solved worse outcomes (ie, better mean scores assess the robustness of the summary
by discussion. If consensus could not be at baseline than at post-intervention), as estimates to determine whether a par-
reached, a third author (ELL) made the the calculation of the PCE entails a log ticular study accounted for the hetero-
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final decision. Interrater agreement was transformation of ratios, not allowing geneity. Thus, to examine the effects of
estimated using Cohen’s kappa statistic.23 for negative values. These values range each result from each study on the over-
Sensitivity analyses were carried out, ex- from 0 to 1, indicating 0% contribution all findings, results were analyzed with
cluding studies with a high-risk bias to from factors not related to the specific each study deleted from the model once.
examine if these trials accounted for signif- intervention itself (PCE = 0) and 100% Finally, the potential moderating effect
Copyright © 2024 Journal of Orthopaedic & Sports Physical Therapy®. All rights reserved.

icant variance in the overall results. Addi- contribution from factors not related to of age at baseline or number of interven-
tionally, the Grading of Recommendations the intervention itself (e.g. nonspecific tion sessions was examined by perform-
Assessment Development and Evaluations effects and contextual effects) (PCE = 1), ing metaregression analyses using the
(GRADE) approach was used to assess the respectively. Since the PCE is intended to Hartung-Knapp-Sidik-Jonkman method.
certainty of evidence. represent proportions and cannot exceed
1 (indicating 100% contribution), val- RESULTS
Summary Measures ues higher than 1 were considered as the

T
A quantitative summary of the data from maximum limit and thus capped at 1 to he electronic search strategy
all included studies was conducted us- maintain the integrity of the interpreta- yielded a total of 4051 studies, and
Journal of Orthopaedic & Sports Physical Therapy®

ing the random-effects inverse-variance tion as a proportion. 68 trials met the inclusion criteria
model with the Hartung-Knapp-Sidik- In studies with more than one treat- (FIGURE 1; list of excluded studies and rea-
Jonkman variance estimator based on ment group, we divided the “shared” sons for exclusion can be found in SUP-
DerSimonian-Laird estimate of tau. We group into two or more subsets with PLEMENTAL FILE 3). Fourteen trials did not
used STATA software (version 17.0; Stata- smaller sample sizes, thereby enabling provide sufficient data for analysis; 54
Corp, College Station, TX, USA) to cal- the analysis of two or more reasonably placebo-controlled trials were included
culate the standardized mean difference, independent comparisons, ensuring that in the meta-analysis. Cohen’s kappa sta-
which was expressed as Hedges’ g with the effects observed in one comparison tistic for interrater reliability was κ = 0.81
95% confidence interval (CI). Changes were not influenced by the same partici- (95% CI: 0.678, 0.941), representing al-
in the outcomes of interest were calcu- pants or data points in another compari- most perfect agreement.
lated by subtracting change differences son. The PCE for each outcome and its
between the intervention and placebo 95% CI was pooled, and subgroup analy- Study Characteristics
groups using the pooled standard de- ses were conducted when at least three The 68 studies included data from 5238
viation (SD) of change in both groups. trials were available. Subgroups includ- participants (mean age: 36.9 ± 11.2 years;
If change scores and SD were not avail- ed type of intervention (ie, dry needling, 59.7% female; SUPPLEMENTAL FILE 4). Sam-
able, they were calculated from 95% con- taping, exercise therapy, manipulation, ple sizes ranged from 23 to 394 indi-
fidence interval (CI) for either change mobilization, soft tissue technique), mus- viduals. Musculoskeletal conditions were
outcome or treatment effect differences culoskeletal condition, and type of pla- predominantly chronic low back pain,
as well as pre-​SD and post-​SD values.3 cebo (ie, manual, nonmanual). Examples chronic neck pain, myofascial pain syn-
The PCE was calculated using the mean of manual placebos were sham manipu- drome, knee/hip osteoarthritis, temporo-
change score of the placebo arm divided lation, sham taping, superficial massage, mandibular disorders, and shoulder pain.
by the mean change score of the interven- sham dry needling (ie, simulation of dry Physical therapy interventions included
tion arm.43,46 Then, this value was log- needling without penetrating the skin), dry needling, taping, manipulation, mo-
transformed to normalize the distribution and nonmanual placebos include the use bilization, soft tissue techniques, neural

journal of orthopaedic & sports physical therapy | volume 54 | number 6 | june 2024 | 393
 [ literature review ]
therapy, and dry needling; SUPPLEMENTAL
FILE 5). The type of treatment with the
largest PCE for pain intensity assessed
immediately after the intervention was
mobilization, which represented 87% of
the overall treatment effect (PCE = 0.87,
95% CI: 0.54, 1.19), followed by soft tis-
sue techniques representing 81% of the
overall treatment effect (PCE = 0.81, 95%
CI: 0.64, 0.97), dry needling with 75%
(PCE = 0.75, 95% CI: 0.36, 1.15), manip-
ulation techniques with 74% (PCE = 0.74,
95% CI: 0.33, 1.14), taping with 69% of
the overall treatment effect (PCE = 0.69,
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95% CI: 0.48, 0.89), and the smallest

proportion not attributable to the specific
intervention itself for pain intensity was
exercise therapy accounting for 46% of
the overall treatment effect (PCE = 0.46,
Copyright © 2024 Journal of Orthopaedic & Sports Physical Therapy®. All rights reserved.

95% CI: 0.41, 0.52).

PCE of Physical Therapy Interventions on
Pain Intensity: Short-Term Effects Three
techniques were not included in the anal-
ysis (mobilization, manipulation, and
taping; SUPPLEMENTAL FILE 6). Moreover,
81% of the overall treatment effects of
manipulation techniques were not attrib-
utable to the intervention itself (PCE =
Journal of Orthopaedic & Sports Physical Therapy®

0.81, 95% CI: 0.61, 1.01), and 73 and 74%

of the overall treatment effects were
FIGURE 1. PRISMA flow diagram of literature search and study selection. PRISMA, Preferred Reporting Items for explained by factors not related to the
Systematic Reviews and Meta-Analyses. intervention itself for mobilization tech-
niques (PCE = 0.73, 95% CI: 0.29, 1.18) and
techniques, and exercise therapy. Placebo through different measurements, includ- taping (PCE = 0.74, 95% CI: 0.53, 0.95),
interventions included manual interven- ing the Visual Analogue Scale or Numeric respectively.
tions such as sham manipulation (ie, Rating Pain Scale. Disability was evaluated PCE of Physical Therapy Interventions on
simulation of the procedure but without using questionnaires, including Oswestry Pain Intensity: Long-Term Effects Only
the rapid application of motion or without Disability Index, Neck Disability Index, manipulation techniques could be in-
thrust), sham taping (ie, placebo neutral Foot and Ankle Disability Index, Constant cluded in the analysis (SUPPLEMENTAL FILE 7),
kinesiotaping without tension), superfi- Shoulder Score, Headache Impact Test, finding that 86% of the overall treat-
cial massage (ie, light touch), asking for Patient Specific Function Scale, Western ment effects were not explained by the
nonrelated active movements, sham dry Ontario and McMaster University, Quebec intervention itself in the long-term (PCE =
needling (ie, simulation of dry needling Pain Disability Index, or Roland-Morris 0.86, 95% CI: 0.76, 0.96). The overall effect
without penetrating the skin), and non- Disability Questionnaire. size of both physical therapy and placebo
manual interventions (ie, detuned devices interventions in the different time points is
like ultrasound, microwave, laser), a com- Summary Measures shown in SUPPLEMENTAL FILES 8-13. The im-
bination of both. One study used unrelat- PCE of Physical Therapy Interventions mediate, short-term, and long-term treat-
ed movements as a placebo intervention.1 on Pain Intensity: Immediate Effects We ment effects in combination with their PCE
The number of treatment sessions analyzed the proportion not attributable for pain intensity is shown in FIGURE 2.
ranged from 1 to 32 (mean: 4.3 ± 5.5 ses- to the specific intervention itself for six PCE of Physical Therapy Interventions on
sions). The effect of physical therapy in- techniques (soft tissue techniques, mo- Pain Intensity by Musculoskeletal Condi-
terventions on pain intensity was assessed bilization, manipulation, taping, exercise tion The analyzed conditions included

394 | june 2024 | volume 54 | number 6 | journal of orthopaedic & sports physical therapy
 Taping 64%
Immediate effects
PCE
Manipulation 40%
Dry needling 74% Specific effects

Mobilization 45%
Taping 69%
0.0 0.5 1.0 1.5 2.0
Manipulation 71% Effect Size (disability)

Mobilization 87% FIGURE 3. Overall treatment effect and the

proportion not attributable to the specific effects
Soft tissue technique 81% (PCE) for disability according to intervention type.
PCE
Exercise 46%
Specific effects
Short-term effects manipulation techniques showed major
asymmetry (LFK = 3.03) and mobilization
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Taping 74%
and taping showed minor asymmetry
Manipulation 81% (LFK = 1.05 and LFK = 1.02, respectively),
suggesting that there might exist under-
Mobilization 74%
representation of studies with negative or
Long-term effects small effects for these outcomes.
Copyright © 2024 Journal of Orthopaedic & Sports Physical Therapy®. All rights reserved.

Manipulation 81% Certainty Assessment and Risk of Bias

The risk of bias analysis is shown in SUPPLE-
0.0 0.5 1.0 1.5 2.0 MENTAL FILE 23. Thirteen studies were at low
Effect Size (pain intensity) risk of bias, 22 were at high risk of bias, and
the remaining 36 studies had some con-
FIGURE 2. Overall treatment effect and the proportion not attributable to the specific effects (PCE) for pain cerns regarding risk of bias. The Cohen’s
intensity in three different time points (immediate, short-term, and long-term) according to intervention type.
kappa statistic for interrater reliability was
κ = 0.971 (95% CI: 0.916, 1.000), repre-
Journal of Orthopaedic & Sports Physical Therapy®

chronic low back pain, chronic neck pain, ability was taping, with 64% of the overall senting almost perfect level of agreement.
myofascial syndrome, knee/hip osteo- treatment effects not explained by the tap- High risk of bias was mainly concentrated
arthritis, neck pain, shoulder pain, and ing intervention itself (PCE = 0.64, 95% in domains of deviations from intended
tension-type headache. Further details are CI: 0.32, 0.96). Similarly, 47 and 40% of interventions, missing outcome data and
presented in SUPPLEMENTAL FILE 14. the overall treatment effect of mobiliza- measurement of the outcome. High risk of
PCE of Physical Therapy Interventions on tion techniques and manipulation tech- bias was found in studies applying taping
Pain Intensity by Placebo Type Seventy niques were not explained by the specific techniques, and low risk of bias was found
percent of the overall treatment effect of tri- effects of those interventions (PCE = 0.47, in studies using mobilization techniques.
als that used a manual placebo were not at- 95% CI: -0.20, 1.13; PCE = 0.40, 95% CI: GRADE assessment showed the overall
tributable to the intervention itself (PCE = 0.01, 0.79, respectively). certainty of the evidence for pain was high
0.70, 95% CI: 0.53, 0.88), and 83% of the Meta Regression The overall PCE was and moderate, and for disability outcomes,
overall treatment effects of the studies that not affected either by the increase in age it was moderate, low, and very low (SUPPLE-
used a nonmanual placebo were not ex- of the participants of the studies (p > .05) MENTAL FILE 24).
plained by the specific effects of the inter- or by the number of sessions of the differ-
vention (PCE = 0.83, 95% CI: 0.54, 1.11; ent interventions (p > .05; SUPPLEMENTAL DISCUSSION
SUPPLEMENTAL FILE 15). Further details are FILE 20).

O
presented in SUPPLEMENTAL FILES 16-18. Sensitivity Analysis and Publication Bias ur findings, which remained
PCE of Physical Therapy Interventions No individual trial had an excessive impact robust after metaregression and
on Disability Regarding disability, four on the pooled effect size of physical therapy sensitivity analysis, indicated that
techniques (mobilization, manipulation, interventions on pain or disability. Visual both nonspecific effects (e.g., natural his-
soft tissue techniques, and taping) were inspection of the doi plots and the LFK in- tory, regression to the mean) and contextu-
included in the analysis (FIGURE 3 and SUP- dex revealed low levels of publication bias in al effects: (1) influenced pain and disability
PLEMENTAL FIGURE 19). The physical therapy terms of pain (SUPPLEMENTAL FILE 21). In in patients with musculoskeletal pain fol-
intervention with the largest PCE for dis- terms of disability (SUPPLEMENTAL FILE 22), lowing physical therapy treatments; (2)

journal of orthopaedic & sports physical therapy | volume 54 | number 6 | june 2024 | 395
 [ literature review ]
had a magnitude dependent on the type PCE values in nonmanual placebo inter- wise, the inclusion of studies published
of treatment considered; and (3) were also ventions, such as detuned electrotherapy only in specific languages might have led
present in sham treatments. devices, compared to manual placebos, us to exclude relevant research conducted
irrespective of the technique employed. A in other languages, potentially skewing
Comparison With Existing Literature possible explanation is the potency of the the overall findings.
The subjective outcomes (pain and dis- treatment ritual associated with these The number of exercise therapy–based
ability) of patients with musculoskeletal interventions, which is likely more pro- studies was small. This was due to the ab-
pain were influenced by different PCE de- nounced than in manual placebos. This sence of placebo groups in exercise thera-
pending on the physical therapy treat- phenomenon may also be attributed to the py studies and the frequent combination
ments considered. This finding is in line perception that nonmanual placebos are of exercise therapy with other interven-
with several previous meta-analyses inves- more technologically advanced and sophis- tions, preventing the isolated examina-
tigating the PCE of treatments in people ticated, enhancing patients’ confidence in tion of exercise therapy effects. Thirdly,
with osteoarthritis9,46 and fibromyalgia,34 the treatment.29 Consequently, patients trials that included disability as an out-
emphasizing that it is the subjective develop higher expectations, leading to come were more likely to report positive
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dimension of suffering experienced by the stronger placebo effects. Similarly, the non- or significant results rather than negative
patient (“illness”) that is more influenced predictable interaction between the spe- or inconclusive findings, thus introducing
by factors not related to the specific inter- cific and contextual effects of treatments potential publication bias.19 Moreover,
ventions rather than the objective one along with the patient’s expectations, pref- our analysis was limited to subjective out-
(“disease”).30,38 Despite the overall consis- erences and beliefs could explain the differ- comes such as pain and disability due to
Copyright © 2024 Journal of Orthopaedic & Sports Physical Therapy®. All rights reserved.

tency reported in the literature, Tsutsumi ent impacts of treatments on outcomes the insufficient number of studies report-
et al.40 reported that the PCE is larger for (pain and disability),29 thus shedding light ing objective outcomes.
objective or semi-objective outcomes, de- on the complexity of the patient’s response There were a lack of data concerning
viating from the general trend. A potential to physical therapy interventions. quality-of-life outcomes in musculoskel-
explanation for this discrepancy could be etal pain interventions. Future research
the heterogeneity of the clinical conditions The Challenge of Factors Not Related should incorporate these outcomes, en-
considered in general medicine (eg, car- to the Specific Intervention in abling a broader assessment of interven-
diovascular and infectious disease) com- Physical Therapy Sham Treatments tions beyond physical symptoms like pain
pared to musculoskeletal pain alone. Factors not related to the specific interven- and disability. Lastly, accurately calculat-
Journal of Orthopaedic & Sports Physical Therapy®

tion itself were also involved in physical ing contextual effects, as previously high-
The Influence of Factors Not Related therapy sham treatments with different lighted,33 is a complex endeavor.
to the Specific Intervention on PCE magnitudes depending on the type The PCE was calculated to assess the
Physical Therapy Treatments of placebo comparator used. This find- extent to which the placebo arm contrib-
Different physical therapy treatments pre- ing indicates the nonexistence of inactive utes to the treatment arm improvement
sented distinct PCE, underlining that the placebo treatments in physical therapy response across different physical thera-
overall outcome cannot be due only to and highlights the challenge of eliminat- py interventions. However, the possible
the specific effects of the intervention.3–6 ing contextual effects from sham physical overestimation of effects not related to
The contextual effects represented, for therapy treatment adopted in the field of the intervention itself by excluding stud-
example, by the ritual of the therapeutic musculoskeletal pain.31 The heterogeneity ies with no change or negative changes
touch of hands-on treatments (eg, mo- of placebo comparators (eg, manual vs in- from baseline values might be consid-
bilization), the use of external devices strumental) revealed by the included stud- ered when interpreting our results. Com-
(eg, taping) and the invasiveness of some ies not only limits the comparison between paring a placebo versus a no treatment
procedures (eg, dry needling), conveying the real and the sham treatments12 but also group allows to isolate contextual effects
a healing meaning,26 can make patients suggests an urgent need to develop and by controlling the nonspecific effects of
aware of the therapy administration and conduct placebo-RCTs following interna- an intervention.8 Unfortunately, due to
influence the outcome itself.30 tional reporting guidelines.19,20 a scarcity of physical therapy RCTs with
untreated control groups, we could not
The Role of Factors Not Related to Limitations analyze the magnitude of the nonspecific
the Specific Intervention in Manual Although we extensively searched eight effects (eg, regression to mean, natural
and Nonmanual Placebos databases, we did not investigate pre- history, and Hawthorne effect).8
Studies in chronic low back pain, chronic published registries, contact experts, or Following the multiplicative model
neck pain, and myofascial pain syndrome conduct gray literature searches, thus in- used for calculating the PCE in previous
populations showed significantly higher troducing a possible selection bias.42 Like- meta-analyses,9,43,46 we assumed all the

396 | june 2024 | volume 54 | number 6 | journal of orthopaedic & sports physical therapy
 improvements in the placebo group as treatment control groups for comparison, Visualization. Enrique Lluch-Girbés:
the sum of nonspecific and contextual ef- and using standardized methodologies. Conceptualization, Methodology,
fects. In fact, despite the term PCE seems Writing - Original draft preparation,
to refer only to contextual effects it refers CONCLUSIONS Supervision. Giacomo Rossettini: Con-
in fact to the combination of nonspecific ceptualization, Methodology, Writing -

N
and contextual effects as reflected when onspecific and contextual ef- Original draft preparation, Supervision.
calculating this metric (treatment versus fects significantly contributed to DATA SHARING: Lirios Dueñas had full
placebo outcomes). the outcomes of physical therapy access to all the data in the study and
interventions for musculoskeletal pain. takes responsibility for the integrity of
Clinical Implications The magnitude of effects not related to the the data and the accuracy of the data
Physical therapists should acknowledge specific intervention itself varies across dif- analysis. The data underlying this article
the impact of factors not related to their ferent physical therapy techniques. These will be shared on reasonable request to
specific treatments and harness their po- results emphasize the pervasive influence the corresponding author.
tential to benefit patients in clinical prac- of factors not related to the specific treat- PATIENT AND PUBLIC INVOLVEMENT: As this
Downloaded from www.jospt.org at on April 12, 2025. For personal use only. No other uses without permission.

tice. Rather than ignoring or trying to ment across various physical therapy inter- meta-analysis involves the synthesis of
control these effects not attributable to ventions, highlighting their critical role in existing data from previously conducted
the intervention itself, physical thera- impacting patient outcomes. t studies, direct involvement of patients
pists can limit them to their advantage was not applicable to the scope of this
when managing musculoskeletal pain.38 KEY POINTS research.
Copyright © 2024 Journal of Orthopaedic & Sports Physical Therapy®. All rights reserved.

During passive treatments, physical ther- FINDINGS: Nonspecific and contextual

apists might tap into contextual effects effects can explain a substantial propor-
by considering the patients’ expectations tion of the immediate, short-term, and REFERENCES
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