Evidence Based Practice Flashcards

Placebo and Nocebo in Evidence-Based Practice

Objectives

• Introduce the concept of placebo.
• Apply understanding of placebo to interpret research outcomes.
• Explore the importance of placebo in clinical practice.
• Recognize and discuss the importance of the comparator in decisions about treatment effectiveness.
• Interpret data from studies using different types of comparators.

Understanding Placebo

• Definition: A sham substance designed to have no therapeutic value.
• Origin: Placebo comes from Latin, meaning 'shall I please?'
• An inert treatment that mimics the active one but has no physiological effects.

Placebo Response/Effect

• Definition: A phenomenon where an otherwise worthless intervention in a study induces an improvement in the patient’s condition or perception of the condition.
• This improvement may be due to the participant's expectation.
• It represents the change in outcome that results from the treatment ritual.

Nocebo Effect

• Definition: Latin for 'to harm'.
• The opposite of the placebo effect, where a negative outcome occurs due to a belief that the intervention will cause harm.

Domains Affected by Placebo

• Changes in self-reported outcomes, which are often the strongest effects:
  • Pain
  • Fatigue
  • Breathlessness
  • Quality of sleep
  • Self-reported function
  • Nausea
• Changes in biomarkers:
  • CSF endorphins
  • Tremor in Parkinson's disease
  • Swelling after wisdom teeth extraction
  • Size of duodenal ulcers on endoscopy
  • Gastric motility
  • Reduction of bronchodilator effect by half when presented as a constrictor.
  • Weight loss when physical work is framed as exercise.

Factors Influencing the Placebo Effect

• Dose-response relationship:
  • One placebo capsule is less effective than two.
  • Four times a day is better than two.
  • Larger capsules are more effective than smaller capsules.
• Ritualistic elements:
  • Tablets with corners are perceived as more effective than round ones.
  • Tablets with colored contents are better than normal pills.
  • More expensive treatments are perceived to have a higher effect.
  • Injections are considered more effective than tablets.
  • Topical applications are preferred over pills.
  • Placebo acupuncture is better than a placebo tablet.
  • Acupuncture is perceived as most effective when provided by a Chinese practitioner.
  • Surgery often tops the list in perceived effectiveness.

Mechanisms of Action

• Treatment expectation:
  • The more a patient thinks a treatment will help, the more it likely will.
  • Expectations of both the client and the therapist play a role.
  • If the control group experiences a nocebo effect, it can enhance the perceived difference.
  • Failed treatment or negative expectations can influence outcomes.
• Research Design:
  • Studies should test whether a treatment provides benefits beyond the ritual of care.
  • All treatments have a placebo component.
  • Design studies to control for the placebo effect.
  • Differentiate between placebo intervention and placebo care.
  • Consider the role of nocebo.

Controlling for the Placebo Response

• Patient blinding
• Standardization between groups
• Credibility of the sham treatment
• Clinical environment
• Equal attention and interaction
• Ensuring the placebo isn't an active treatment
• Checking for blinding at the end
• Therapist blinding
• Equal enthusiasm and engagement
• Checking for blinding
• To measures size of placebo effect in a study a 3 arm trial is needed

Clinical Practice Implications

• The placebo effect is real and can lead to significant changes.
• It is an inescapable part of care.
• Clients can benefit from optimizing non-specific effects.
• It is never okay to apply nonsense treatments.
• It is important to be trustworthy and competent.
• Give adequate attention.
• Examine thoroughly.
• Explore patients' views and legitimize concerns.
• Reassure and explain.
• Take time with patients.

Therapist's Attitude and Clinical Outcome

• Study on lumbar facet joint injections:
  • Patients in the experimental group (EG) had a conversation with the radiologist and were shown images after the injection.
  • The control group (CG) left the clinic without further contact.
  • The EG showed a statistically significant reduction in pain at 1 week and 1 month post-treatment, but no significant differences at 3 and 6 months.

Nocebo in Clinical Practice and Research

• Adverse events or outcomes related to negative expectations or anticipations/beliefs.
• Can occur through:
  • Priming via side-effects listing
  • Priming via expectation of pain
  • Language and words used
  • Diagnostic labeling
  • Clinician demeanor

Comparators in RCTs

• Treatment effect needs to be interpreted considering the comparator.
• The ideal control is a credible placebo.
• Different comparators provide different information.

Types of Comparators

• Sham (Placebo):
  • Should be inert with no discernible physiological effect.
  • Should be realistic, making the patient feel they are receiving care.
  • Clinicians should be blinded to which treatment is real.
• Sham (Placebo) + Natural History:
  • Includes a natural history arm for additional comparisons.
• Usual Care:
  • Compares a new treatment to what is already done.
  • Often done if not ethical to 'do nothing'.
  • Natural history not accounted for.
  • Can have unbalanced treatment.
  • Does not control for non-specific effects.
• Natural History:
  • Treatment arm receives non-specific effects and any potential treatment effect.
  • Natural History group often sit on a waitlist.
  • Relevant for acute conditions or recurrent episodes.
  • Informs decisions about whether the benefits of treatment A are worth the costs, risks, and inconvenience beyond natural recovery.
• Nocebo:
  • What if the comparator is harmful?

Key Concepts Summary

• Different comparators in clinical trials provide different information.
• Sham (placebo) is best, ideally with a natural history group as well.
• Note the different things we learn from:
  • Sham
  • Usual care
  • Natural History
  • Nocebo