Quantifying the Placebo Effect in Psychological Outcomes of Exercise Training: A Meta-Analysis

[Dolphin]

http://link.springer.com/article/10.1007/s40279-015-0303-1

Thought there was a chance this might be interesting. Don't have the full text myself.

They do reference a few CFS papers:

1. Edmonds M, McGuire H, Price J. Exercise therapy for chronic fatigue syndrome. Cochrane Database Syst Rev. 2004;(3):CD003200.
2. Edmonds M, McGuire H, Price JR. Exercise therapy for chronic fatigue syndrome. Cochrane Libr. 2013;8:1–19.
3. Castell BD, Kazantzis N, Moss-Morris RE. Cognitive behavioral therapy and graded exercise for chronic fatigue syndrome: a meta-analysis. Clin Psychol Sci Pract. 2011;18:311–24
4. Cho HJ, Hotopf M, Wessely S. The placebo response in the treatment of chronic fatigue syndrome: a systematic review and meta-analysis. Psychosom Med. 2005;67(2):301–13.

Quantifying the Placebo Effect in Psychological Outcomes of Exercise Training: A Meta-Analysis of Randomized Trials

Jacob B. Lindheimer,
Patrick J. O’Connor,
Rod K. Dishman

Abstract

Background

The placebo effect could account for some or all of the psychological benefits attributed to exercise training.

The magnitude of the placebo effect in psychological outcomes of randomized controlled exercise training trials has not been quantified.

The aim of this investigation was to estimate the magnitude of the population placebo effect in psychological outcomes from placebo conditions used in exercise training studies and compare it to the observed effect of exercise training.

Methods

Articles published before 1 July 2013 were located using Google Scholar, MEDLINE, PsycINFO, and The Cochrane Library.

To be included in the analysis, studies were required to have (1) a design that randomly assigned participants to exercise training, placebo, and control conditions and (2) an assessment of a subjective (i.e., anxiety, depression, energy, fatigue) or an objective (i.e., cognitive) psychological outcome.

Meta-analytic and multi-level modeling techniques were used to analyze effects from nine studies involving 661 participants.

Hedges’ d effect sizes were calculated, and random effects models were used to estimate the overall magnitude of the placebo and exercise training effects.

Results

After adjusting for nesting effects, the placebo mean effect size was 0.20 (95 % confidence interval [CI] −0.02, 0.41) and the observed effect of exercise training was 0.37 (95 % CI 0.11, 0.63).

Conclusion

A small body of research suggests both that (1) the placebo effect is approximately half of the observed psychological benefits of exercise training and (2) there is an urgent need for creative research specifically aimed at better understanding the role of the placebo effect in the mental health consequences of exercise training.

http://link.springer.com/search?facet-author="Rod+K.+Dishman"

 

[Esther12]

Looks interesting. They included fatigue and pain as psychological outcomes. I can't find a copy of it available.

 

[Denise]

Thanks for finding this abstract.
I agree that this looks like an interesting read.

 

[Esther12]

I've just got a copy. I don't think that this paper is going to be particularly revelatory for most people here, and the limited evidence available made it difficult for the authors to provide really interesting results for us. It's good to see some of these problems being acknowledged, but I'm not sure that their recommendations for the future are that great. It is a difficult problem to overcome though, and I think that the most important change needed is ensuring that researchers and clinicians are always open about the problems with the research that underpins their claims about the value of exercise interventions.

They note the problem of a failure to account for placebo effects leading to exaggerated claims about the value of exercise.

They examine trials which have a 'real' exercise intervention and then a 'placebo' exercise intervention for which there is no good evidence of possible efficacy (eg: light hand exercises). I'm concerned that such 'placebo' interventions are less likely to induce bias and placebo effects than 'real' exercise interventions, and also, for CFS there has been a trend for GET promoters to try to argue (now that they've been busted over claims of fitness, activity levels, etc) that the 'real' value of exercise is in introducing patients to activity, and helping them overcome fears of it.

The rest of this post is really just my notes and quotes I pulled out. The paper's 19 pages, so some won't want to read the whole thing themselves.

Exercise training interventions
often include questionnaires or other measures of psychological
outcomes that may be especially open to biases
introduced by demand characteristics [14] and
experimental artifacts such as the placebo effect [15, 16].
Double-blind designs are not possible in exercise training
studies [17]; however, placebo groups have at times been
used to assess the placebo effect.

Based on prior research, we hypothesized that placebo
effects would be (1) present in both subjective and objective
outcomes [1, 62], (2) larger with greater exposure to
the placebo condition [63], and (3) moderated by placebo
type [64].

2.2 Study Selection
Studies were included in the analysis when the following
criteria were met: (1) English language, (2) designed as a
randomized trial with participants allocated to an exercise
treatment arm, a control arm, and an arm that we or the
authors classified as a placebo, (3) the treatment group
engaged in at least 4 weeks of exercise training, (4) exercise
training was not included as an adjuvant to another
treatment, (5) the placebo group received an inert intervention
for the outcome measure being reported, and (6)
outcome data were reported for anxiety, cognitive performance,
depression, energy, or fatigue.

The operational definitions for placebo interventions are
inconsistent [9, 10, 66–71]. Here, a placebo intervention
was defined as an intervention that was not generally recognized
as efficacious, that lacked adequate evidence for
efficacy, and that has no direct pharmacological, biochemical,
or physical mechanism of action according to the
current standard of knowledge [72]. Physical activity that
involved small muscle groups (e.g., hand or facial movements)
or very low intensities (e.g., B40 % peak) was
classified as an exercise placebo condition. Convincing
evidence that documents that psychological improvements
result from these types of exercise stimuli is lacking. Some
past meta-analyses have considered any intervention
defined as a placebo by the study authors to be a valid
placebo [9], but that approach was flawed for the present
analysis. Instead, we verified that placebo groups did not
receive an intervention that was later discovered to be
efficacious for the outcome being studied. For instance,
two early studies assigned participants to a ‘placebo’
strength and flexibility program [73, 74]. However, those
studies were not included in the present analysis since it
has been determined that resistance exercise can influence
certain psychological outcomes [75].

They had a difficult job to do, but to me it sounds like the exercise interventions are more likely to lead to problems with bias than their placebo controls, so this review will only be able to say that certain unusually limited types of exercise intervention are associated with certain changes in questionnaire scores.

This could still be interesting though:

To determine whether aggregated effect sizes varied according
to heterogeneity between studies and to gain a
better understanding of the literature [96], characteristics of
each investigation were recorded in a spreadsheet and
coded for moderator analysis. Potential moderators of
placebo effects were selected to describe characteristics of
a given study that could contribute to a heterogeneous effect
size. The moderators were selected based on relevant
literature [8–10] and availability of data. The three selected
primary moderators were outcome type, total minutes of
exposure to the placebo intervention, and the type of
placebo intervention.

...

Secondary moderators of placebo
included the following: placebo intervention session duration,
daily frequency of exposure to the placebo intervention,
placebo intervention program length, whether
placebos were administered in a group or individual setting,
blinding of test administrators to group allocation,
type of control comparison, whether intent-to-treat analysis
was used, whether the participant samples were clinical
patients, whether the study outcome was reported as primary
or secondary, the year of publication, and the geographic
location of the study.

No CFS studies were included.

3.2.2 Primary Moderator Analysis [For placebo exercise over control]:
The overall meta-regression model was significant
(QR3 = 19.36; p = 0.0002; R2 = 0.39; QE44 = 29.81;
p = 0.95). Outcome type (b = 0.19; z = 3.65;
p = 0.0003) significantly contributed to the total variation
of the effect of placebo interventions on psychological
outcomes. Effects were larger when subjective outcomes
were measured (D = 0.31; 95 % CI 0.12, 0.42) compared
with objective outcomes (D = -0.02; 95 % CI -0.15,
0.10).
In the multi-level model, outcome type (beta = 0.193,
SE = 0.050, z = 3.85, p\0.001) and placebo type (beta
= -0.139, SE = 0.063, z = 2.21, p = 0.027) improved
model fit (v2 (4) = 119.8, BIC = 123) compared with the
intercept-only model (Dv2 (2) = -356.8, p\0.001).
There was zero residual variance (z = 0.06, p = 0.956),
indicating that all of the variance between effects was
explained by these two moderators.

3.2.4 Primary Moderator Analysis [For exercise intervention over control]
The overall meta-regression model was significant
(QR3 = 20.17; P = 0.0002; R2 = 0.34; QE37 = 38.33;
p = 0.41). Outcome type (b = 0.17, SE = 0.05, z = 3.25,
p = 0.001) and exercise type (b = -0.20, SE = 0.08,
z = -2.39, p = 0.017) were related to effect size. Effects
were larger when (1) subjective outcomes were measured
(D = 0.47; 95 % CI 0.28, 0.67) compared with objective
outcomes (D = 0.08; 95 % CI -0.03, 0.19) and (2) when
combined exercise interventions were used (D = 0.52;
95 % CI 0.31, 0.72) compared with interventions that used
resistance exercise (D = 0.08; 95 % CI -0.04, 0.42) or
walking exercise (D = 0.30; 95 % CI 0.05, 0.54).
In the multi-level model, outcome type (beta = 0.143,
SE = 0.058, z = 2.45, p = 0.014) and exercise type (beta
= -0.135, SE = 0.050, z = 2.70, p = 0.007) improved
model fit (v2 (4) = 117.2, BIC = 120) compared with the
intercept-only model (Dv2 (2) = -21.08, p\0.001).
There was zero residual variance (z = 0.10, p = 0.923),
indicating that all of the variance between effects was
explained by these two moderators (i.e., variance in the
conditional model including study duration/variance in the
intercept only model).

From their discussion:

4.2 Placebo Effect
After adjusting for nesting effects, the magnitude of the
mean population placebo effect in psychological outcomes
from placebo conditions used in exercise training studies
was estimated to be D = 0.20. A key novel finding of this
investigation is that the mean placebo effect was about half
of the observed psychological benefits of exercise training.
Put another way, when the placebo effect (D = 0.20) was
subtracted from the observed effect of exercise (D = 0.37),
the true effect of exercise training on psychological
outcomes was estimated to be D = 0.17. Therefore, the
true effect of exercise training per se on psychological
outcomes is likely to be substantially smaller than those
suggested in previous reviews that have ignored the
potential placebo effect [19, 28, 34].

Other authors have explicitly recognized that exercise
training effects are attenuated when comparisons are made
with placebo groups [58, 100]. These observations combined
with the present findings underscore the usefulness of
including both control and placebo groups in experimental
designs aimed at understanding the true effect of exercise
on psychological outcomes. Previous studies that restricted
participant allocation to an experimental and control group
presumably show effects attributed to exercise training that
may well be conflated by non-exercise variables that are
part of the psychosocial situation in which exercise takes
place, including variables such as participant expectations—
the predominant hypothesized mechanism of the
placebo response [101, 102].

It is unclear why the placebo effect became non-significant
in the multi-level model, but controlling for nesting
effects revealed that some placebo treatments had a negative
effect on psychological outcomes, which resulted in a
wider range of the CI around the mean effect. Most of the
nested effects came from a study that examined the influence
of exercise training on objective measures of cognitive
performance, and more studies would have enhanced
the statistical power of this analysis.

I don't think that this is surprising, but might be worth keeping as a reference to cite/quote, although overall I'm not sure how helpful the paper is:

4.2.2 Outcome Type

The placebo effect was substantially moderated by outcome
type before and after controlling for nesting effects.
Outcomes that were classified as subjective (e.g., anxiety,
depression, energy, fatigue) showed larger effects than did
objective outcomes (e.g., performance on cognitive tests).
Therefore, studies that measure the impact of exercise on
subjective psychological outcomes appear to be especially
susceptible to placebo effects. While this seems plausible,
others have found similar sized placebo effects when
comparing subjective and objective outcomes [103, 104].
No studies yet have addressed this question using subjective
and objective measures calibrated to be equally sensitive
to change with exercise. It would have been useful to
determine whether the size of the placebo effect varied
between the different types of subjective outcomes or
domains of cognition, but there were not enough data to
conduct a meaningful analysis.

I thought that this was interesting:

Less than 2 % of the studies that were assessed for eligibility
were placebo-controlled experiments with a concomitant
control group. Moreover, the most recent study to
meet the inclusion criteria was published in 2009, which is
4 years prior to the start of the literature search [99].
Potential reasons for the infrequent use of placebos in
exercise training studies include ethical concerns [62], the
lack of consensus as to what constitutes an appropriate
placebo condition for exercise, and the inability to include
a placebo group due to insufficient resources. The type of
placebo groups that were used varied substantially; this
was illustrated by the fact that no two studies used identical
placebo conditions. Our analysis suggested that ‘very lowintensity
exercise’ placebos showed the largest placebo
effects, but only two studies used placebo interventions that
could be categorized in that way.

Their recommendations for the future:

4.4 Future Research
The present findings are consistent with the robust placebo
effects reported in research and clinical settings. The
results reported here suggest that placebo effects play a
substantial role in the psychological outcomes of exercise
training. Ultimately, placebo effects might be important in
elucidating the psychological benefits of regular physical
activity from the perspectives of explanatory mechanisms
and the optimization of the benefits in clinical settings.
However, there are numerous gaps that need to be addressed
in order for placebo effects that may accompany
exercise training to be fully understood.
It is recommended that future studies include placebo
groups in randomized controlled trials that are designed to
examine the psychological effects of exercise. Conditions
that resemble some aspects of very low-intensity exercise
include equipment that moves the limbs of an individual
(passive exercise) [109], low-intensity electrical stimulation
of muscle [110], hypnotic suggestion of exercise [111],
and imagery of exercise [112]. Choices regarding the
characteristics of an exercise placebo could be tailored to
the psychological outcome being investigated. It is
important to ensure that an ‘exercise placebo’ is truly inert
and has not been proven to be an effective therapy, but is
also administered in a psychosocial context that is believable
to a participant; otherwise expectations may not be
influenced [62]. Exploratory research that evaluates the
magnitude of the treatment and expectancy response to
different types of potential placebo conditions (e.g., passive
exercise, low-intensity electrical stimulation, hypnotic
suggestion of exercise, imagery of exercise, social contact,
relaxation, sugar pills, sham ultrasound, sham acupuncture)
compared with an exercise training and no-treatment control
group is needed to help determine the advantages and
disadvantages of various approaches for placebo groups in
exercise training studies in which the focus is on psychological
outcomes.

On pain:

Exercise training appears to improve pain symptoms,
but this could be largely caused by placebo effects [115–
140]. No study with a pain outcome measure met the criteria
to be included in the present analysis. One study that
was considered included exercise training, control, and
placebo groups but did not provide sufficient information
to allow extraction of effects [141]. Placebo analgesia is a
frequently researched topic in the placebo literature, and
the largest placebo effects often are realized with pain
outcome measures [64]. Studies with placebo and control
groups that focus on the effects of exercise training on pain
are needed.

Their conclusion:

5 Conclusion
Exercise training trials focused on psychological outcomes
that include placebo and control groups are urgently
needed to augment our understanding of both placebo
responses and the true effect attributable to exercise
training per se. The small body of studies reviewed here
suggests that the effect of exercise on psychological outcomes
is considerably smaller after accounting for the
placebo effect. Placebo effects appeared to be stronger
when subjective outcomes were measured and when ‘very
low-intensity exercise’ placebos were used. Researchers
should consider using this information to guide their own
interpretation of previous and future studies.

 

[Sean]

The small body of studies reviewed here
suggests that the effect of exercise on psychological outcomes
is considerably smaller after accounting for the
placebo effect. Placebo effects appeared to be stronger
when subjective outcomes were measured...

Useful statement.

(Not sure if psychological outcomes include any subjective self-report measure of physical capacity. I would think so, but others may not...)

 

[Esther12]

Useful statement.

(Not sure if psychological outcomes include any subjective self-report measure of physical capacity. I would think so, but others may not...)

They listed these as subjective outcomes from Tench et al. [86]. (Co-authored with PD White).

Fatigue Chalder Fatigue Scale 1
Fatigue Severity Score 1
Visual Analog Scale 1
Vitality SF-36 Vitality Scale

Study here: http://rheumatology.oxfordjournals.org/content/42/9/1050.full

They said:

functional status was measured using the Medical Outcomes Study Short‐Form Health Survey (SF‐36) [18]

So it looks like the SF36-PF PF scale was not counted as subjective:

Key findings
Graded exercise therapy leads to significantly greater overall improvement than relaxation therapy or no intervention using intention‐to‐treat analysis. There was a trend for the subsidiary outcome of fatigue to improve with exercise therapy, but this was significant on only one of the three fatigue measures. This may reflect insensitivity of the fatigue measures used or lack of statistical power to detect a change. Improvements in fatigue were not maintained at the 3‐month follow‐up, and this may be explained by the fact that only eight patients continued to exercise at the end of supervised therapy. The fact that those patients who continued to exercise after the intervention period had significantly lower fatigue scores compared with those who stopped exercising suggests it is the continuation of exercise that leads to a sustained improvement.

It is interesting that the SF‐36 vitality and role physical scales showed significant improvements after exercise therapy at the 3‐month follow‐up. However, the fact that this was not seen the end of the 12‐week intervention period suggests this may not be a reliable finding and may simply reflect sample attrition.

Exercise duration increased by 18% after exercise therapy compared with a 3% reduction in the no intervention group, but there was no significant change in aerobic fitness. This change in exercise duration is likely to be due to improved exercise tolerance and is important because improved exercise capacity may reflect improvements in physical disability. However, this was not supported by any significant changes in self‐perceived measures of physical function. There was no flare in disease activity with exercise and there were no serious adverse events.

Also, looking at this placebo study again reminded me that they released quite a lot of data I did not really go through. I only focussed on the main findings that they discussed.

 

[user9876]

T


So it looks like the SF36-PF PF scale was not counted as subjective:

I can see an argument that says it is not subjective in that it asks questions about how you cope with different defined physical activities. However, unless you test people then the answers are perceptions of the individual at the time around how easy/hard an activity is. A couple of the questions are quite vague as well. So to improve a score you only need to change someones perception of the ease of an activity rather than how they can actually cope. Hence in reality it is subjective.

An extra complexity comes in with ME in that someone may answer to say they have no problems walking several blocks and no problems climbing several flights of stairs. But the survey doesn't capture the idea that both couldn't be done on the same day or that there would be a long recovery time with PEM. Again this is an area where peoples perceptions may change or they could be encouraged to fill out a questionnaire differently.

 

[Sean]

So it looks like the SF36-PF PF scale was not counted as subjective:

Well, that is a problem right there. It is clearly subjective.