Placebo effect: a psychosomatic component, or only an aggregate of other biases?

Review on placebo injections on Knee Osteoarthritis -- not sure whether it warrants an own thread. Thought Edzards' Ernst blog article including others' comments could be interesting;

Previtali D, Merli G, Di Laura Frattura G, Candrian C, Zaffagnini S, Filardo G. The Long-Lasting Effects of "Placebo Injections" in Knee Osteoarthritis: A Meta-Analysis. Cartilage. 2021 Dec;13(1_suppl):185S-196S. doi: 10.1177/1947603520906597. Epub 2020 Mar 18. PMID: 32186401; PMCID: PMC8808779.

Free PMC full text:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8808779/

Abstract

Objectives

To quantify the placebo effect of intraarticular injections for knee osteoarthritis in terms of pain, function, and objective outcomes. Factors influencing placebo effect were investigated.

Design

Meta-analysis of randomized controlled trials; Level of evidence, 2. PubMed, Web of Science, Cochrane Library, and grey literature databases were searched on January 8, 2020, using the string: (knee) AND (osteoarthritis OR OA) AND (injections OR intra-articular) AND (saline OR placebo). The following inclusion criteria were used: double-blind, randomized controlled trials on knee osteoarthritis, including a placebo arm on saline injections. The primary outcome was pain variation. Risk of bias was assessed using the RoB 2.0 tool, and quality of evidence was graded following the GRADE (Grading of Recommendations Assessment, Development and Evaluation) guidelines.

Results

Out of 2,363 records, 50 articles on 4,076 patients were included. The meta-analysis showed significant improvements up to the 6-month follow-up: Visual Analogue Scale (VAS)-pain −13.4 mean difference (MD) (95% confidence interval [CI]: −21.7/−5.1; P < 0.001), Western Ontario and McMaster Osteoarthritis Index (WOMAC)-pain −3.3 MD (95% CI: −3.9/−2.7; P < 0.001). Other significant improvements were WOMAC-stiffness −1.1 MD (95% CI: −1.6/−0.6; P < 0.001), WOMAC-function −10.1 MD (95% CI: −12.2/−8.0; P < 0.001), and Evaluator Global Assessment −21.4 MD (95% CI: −29.2/−13.6; P < 0.001). The responder rate was 52% (95% CI: 40% to 63%). Improvements were greater than the “minimal clinically important difference” for all outcomes (except 6-month VAS-pain). The level of evidence was moderate for almost all outcomes.

Conclusions

The placebo effect of knee injections is significant, with functional improvements lasting even longer than those reported for pain perception. The high, long-lasting, and heterogeneous effects on the scales commonly used in clinical trials further highlight that the impact of placebo should not be overlooked in the research on and management of knee osteoarthritis.


Edzard Ernst's take on the authors' conclusion:

https://edzardernst.com/2022/08/effects-of-placebo-injections-in-knee-osteoarthritis/


Mind that one of the commenters on Ernst's blog who seems to make some reasonable points might have her own blind spots with regard to what seems to be her hobbyhorse -- developing a hypothesis and offering a treatment of "non-malignant chronic pain without sufficient explanatory pathology".

It's fair to stress though that I don't think she uses her comments to promote her treatment or even just her ideas about that.

 

I see we have reached the No true placebo stage. Neat.

In other words, button soup consists of meat, vegetables, broth, herbs and spices. Also a button.

Having such ridiculously large effect sizes really should clue in people that this is obviously invalid data. May as well believe in the actual healing power of kisses from mama on a booboo. But nope, magical thinking is that powerful. Not powerful enough to have the effect people attribute to "placebo", but definitely enough for people to believe that such a magical thing must exist, because otherwise the world out there is bleak and scary and beyond our control and so so stressful. Pfft.

 

Even if they did, they still can't control for response bias.

 

There is also an assumption that injecting someone with saline is a non treatment. This is not the same as eating a bit of sugar that looks like a pill.

 

There is a new German podcast episode about placebo/nocebo effects. (German public broadcasting) The power of expectation - placebo and nocebo effects.
The main author has become well known for a very good and the most listened Corona podcast in Germany.

This podcast is unfortunately very uncritical about claims how powerful placebo/nocebo effects are: You can get very ill from Google and medication leaflets.

We must try to use placebo effects to make therapies more effective. Open placebos also help. etc.. It is presented as a scientific consensus. Placebo scientists and a neurologist who wrote a book about the powerful nocebo effect are interviewed.

https://www.ardaudiothek.de/episode...tung-placebo-und-nocebo-effekte/ndr/12478073/