More notes on the placebo effect

I can't find a damn article about the possibilities the placebo effect is caused by body systems which respond to talking and healer behaviour.

So I'm wandering around the web looking for more information and not getting far. My head's really starting to hurt to understand the following paper.

Evidence for placebo effects on physical but not on biochemical outcome parameters: a review of clinical trials
Karin Meissner , Hans Distel  and Ulla Mitzdorf
BMC Medicine 2007, 5:3doi:10.1186/1741-7015-5-3
http://www.biomedcentral.com/1741-7015/5/3

So after filtering out a low of studies the authors found a few select ones which allowed them to compare placebo control group effect sizes with those who got no treatment at all. The results are that certain types of research measures, "physical parameters", have a significant placebo effect where as body systems, "biochemical processes", don't. The review excluded all psychological, neurological and psychiatric papers. It purely looked at physical medicine.

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The explorative analysis revealed that significant placebo effects were predominantly found for parameters measuring physical processes, e.g., blood pressure, or forced expiratory volume in 1 second (FEV₁). Therefore, all types of physical outcome parameters were collected in one class, which was named "physical parameters". The remaining parameters, less frequently responding to placebo treatments, appeared to represent biochemical processes measured in peripheral body fluids and tissues, e.g., cholesterol and cortisol. Therefore, they were all taken together in one alternative class, which was named "biochemical parameters". To be more precise, 8 of 16 trials (50%) using physical parameters as outcomes reported significant placebo effects compared with only 1 of 18 trials (6%) using biochemical parameters. This difference was statistically significant (Fisher's exact probability test, P < 0.01).

To further substantiate this classification, we performed subanalyses for both groups of parameters. This revealed a significant placebo effect for physical parameters with a pooled effect size of g = 0.34 (95% CI 0.22 to 0.46, P < 0.0001), but an effect size close to zero for biochemical parameters (g = 0.03, 95% CI -0.04 to 0.10, P = 0.41) (see Figure 1). The differentiation between physical and biochemical parameters reduced heterogeneity (χ² = 24.63, P = 0.03, I² = 47.2%; and χ² = 6.39, P = 0.96, I² = 0%, respectively). Sensitivity analyses revealed that heterogeneity within the group of physical parameters was due to one outlier [20], and the exclusion of this study substantially reduced heterogeneity (I² = 0%).

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Here's a useful bit of the discussion.
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Our results indicate that placebo interventions can improve objective measures of peripheral disease processes. They furthermore suggest that placebo interventions do not improve all kinds of peripheral outcome parameters equally, but primarily those reflecting physical disease processes.

The meta-analysis of placebo effects in the first dataset (collected from a MEDLINE search for placebo-controlled clinical trials) revealed a significant overall improvement of peripheral outcome parameters by placebo treatments. The explorative analysis indicated that significant effects occurred more frequently on physical than on biochemical parameters. Accordingly, an overall placebo effect across trials was only found within the subgroup of physical parameters. In comparison to the pharmacological medication, the administration of placebos improved physical parameters on average by one-third – a remarkable efficacy, not found for biochemical parameters. These results already suggest that placebo interventions affect physical parameters more frequently and strongly than biochemical parameters.

However, our classification was derived from clinical placebo-controlled trials without a no-treatment arm. These trials had not been designed to analyze placebo effects but to estimate the effect of the active medication against placebo control groups. Therefore, factors not due to placebo treatment may have contributed to the changes in the placebo groups in such trials, e.g., the natural course of the disease, and regression to the mean. We attempted to control for these factors by focusing on trials with otherwise stable disease conditions and tried to minimize the risk of regression to the mean by excluding trials on non-random samples selected by screening from a healthy population [68]. However, even in stable chronic conditions, symptoms may vary over time, and the possibility that some of the improvement on physical parameters may be due to regression cannot be fully excluded by the present data.

Therefore, to further substantiate our classification, we made use of the database of Hróbjartsson and Gøtzsche, which contains a complete collection of trials including both a placebo and a no-treatment control group [5,6]. Again, the subanalysis of trials with peripheral outcome parameters revealed a significant improvement from placebos compared with no treatment for the subgroup of physical parameters only. In fact, the analysis even showed a significant negative effect of placebos on biochemical parameters. However, as the number of trials reporting on biochemical parameters was small, this finding should be treated with caution.
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And here's the sort of gold I was looking for. This is what I find interesting about the placebo effect and the possibilities for healthcare and other areas of life.
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One frequently discussed mediating mechanism of placebo effects is the patient's expectation of clinical improvement, which can be raised, for example, by verbal suggestions accompanying placebo treatment [79,80]. Expectation and operant conditioning may complement each other. Learning theory emphasizes the importance of response-specific expectations for the performance of operant conditioning tasks [81]. Thus, the patient may direct his/her attention to symptom improvement because he/she is expecting a clinical benefit. In this sense, expectation may be necessary to both initiate and maintain the process of operant conditioning. It has recently been demonstrated that in patients with parkinsonian disease, both the expectation and the actual experience of a clinical benefit during placebo treatment activates the inner-brain reward circuitry [74,82]. This experimental result fits well with the hypothesis that both mechanisms (expectation and operant conditioning) are involved in the mediation of placebo effects.
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The conclusions are interesting.
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Our results indicate that placebo treatments of peripheral disease processes can affect physical parameters more easily and strongly than biochemical parameters. This differentiation holds true for both datasets we tested, i.e., conventional placebo-controlled clinical trials, and clinical trials that included a no-treatment arm. As a corollary, it follows that placebo-responsive subgroups may also be identified in datasets in which global averages conceal such specific responses.

Although much progress has been made in the past decade in understanding the biological basis of placebo effects in neurological conditions, e.g., pain and parkinsonian disease, the mechanisms that mediate placebo effects on peripheral organ systems still await to be further elucidated. The differential placebo responsiveness of physical versus biochemical parameters, as disclosed in the present study, offers a good starting point for theoretical considerations on possible mediating mechanisms, as well as for future investigations in this field.
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