scholarly journals European Headache Federation recommendations for placebo and nocebo terminology

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Dimos D. Mitsikostas ◽  
◽  
Charlotte Blease ◽  
Elisa Carlino ◽  
Luana Colloca ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Working Group ◽  
Medical Condition ◽  
Placebo Response ◽  
Placebo Administration ◽  
Nocebo Effect ◽  
Nocebo Effects ◽  
Final Agreement ◽  
European Headache Federation ◽  
Term Response

Abstract Background and aim Despite recent publications, practitioners remain unfamiliar with the current terminology related to the placebo and nocebo phenomena observed in clinical trials and practice, nor with the factors that modulate them. To cover the gap, the European Headache Federation appointed a panel of experts to clarify the terms associated with the use of placebo in clinical trials. Methods The working group identified relevant questions and agreed upon recommendations. Because no data were required to answer the questions, the GRADE approach was not applicable, and thus only expert opinion was provided according to an amended Delphi method. The initial 12 topics for discussion were revised in the opinion of the majority of the panelists, and after a total of 6 rounds of negotiations, the final agreement is presented. Results/recommendations Two primary and mechanism-based recommendations are provided for the results of clinical trials: [1] to distinguish the placebo or nocebo response from the placebo or nocebo effect; and [2] for any favorable outcome observed after placebo administration, the term “placebo response” should be used, and for any unfavorable outcome recorded after placebo administration, the term “nocebo response” should be used (12 out of 17 panelists agreed, 70.6% agreement). The placebo or nocebo responses are attributed to a set of factors including those that are related to the medical condition (e.g. natural history, random comorbidities, etc.), along with idiosyncratic ones, in which the placebo or nocebo effects are attributed to idiosyncratic, or nonspecific mechanisms, exclusively (e.g. expectation, conditioning, observational learning etc.). To help investigators and practitioners, the panel summarized a list of environmental factors and idiosyncratic dynamics modulating placebo and nocebo effects. Some of them are modifiable, and investigators or physicians need to know about them in order to modify these factors appropriately to improve treatment. One secondary recommendation addresses the use of the terms “placebo” and “nocebo” (“placebos” and “nocebos” in plural), which refer to the triggers of the placebo/nocebo effects or responses, respectively, and which are inert agents or interventions that should not be confused with the placebo/nocebo responses or effects themselves (all panelists agreed, 100% agreement). Conclusion The working group recommends distinguishing the term response from effect to describe health changes from before to after placebo application and to distinguish the terms placebo(s) or nocebo(s) from the health consequences that they cause (placebo/nocebo responses or effects).

scholarly journals Unethical informed consent caused by overlooking poorly measured nocebo effects

2020 ◽  
pp. medethics-2019-105903
Author(s):  
Jeremy Howick
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Informed Consent ◽  
Natural History ◽  
Adverse Events ◽  
Placebo Effect ◽  
Nocebo Effect ◽  
Control Groups ◽  
Nocebo Effects ◽  
Negative Outcome

Unlike its friendly cousin the placebo effect, the nocebo effect (the effect of expecting a negative outcome) has been almost ignored. Epistemic and ethical confusions related to its existence have gone all but unnoticed. Contrary to what is often asserted, adverse events following from taking placebo interventions are not necessarily nocebo effects; they could have arisen due to natural history. Meanwhile, ethical informed consent (in clinical trials and clinical practice) has centred almost exclusively on the need to inform patients about intervention risks with patients to preserve their autonomy. Researchers have failed to consider the harm caused by the way in which the information is conveyed. In this paper, I argue that the magnitude of nocebo effects must be measured using control groups consisting of untreated patients. And, because the nocebo effect can produce harm, the principle of non-maleficence must be taken into account alongside autonomy when obtaining (ethical) informed consent and communicating intervention risks with patients.

Placebo and nocebo effects in randomized double-blind clinical trials for fatigue in advanced cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9640-9640
Author(s):  
M. de la Cruz ◽  
D. Hui ◽  
H. A. Parsons ◽  
P. Lynn ◽  
C. Parker ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Cancer Patients ◽  
Advanced Cancer ◽  
Randomized Clinical Trials ◽  
Placebo Response ◽  
Well Being ◽  
Advanced Cancer Patients ◽  
Edmonton Symptom Assessment Scale ◽  
Nocebo Effects

9640 Background: We have previously reported significant placebo response in randomized controlled treatment trials for cancer related fatigue (CRF). We conducted a retrospective study to determine the frequency and predictors of response to placebo and nocebo effect in patients with CRF. Methods: We reviewed patients that received placebo in two previous randomized clinical trials conducted by our group and determined the proportion of patients who demonstrated clinical response to fatigue using an increase (ΔFACIT-F score) > 7 from baseline to day 8, and those with nocebo response as those who reported side effects. Baseline patient characteristics and symptoms recorded from the Edmonton Symptom Assessment Scale (ESAS) were analyzed to determine their association with placebo and nocebo effects. Results: A total of 105 advanced cancer patients received placebo. 59 (56%) patients responded to placebo (median Δ FACIT-F score of 22). Worse baseline anxiety and well-being subscale score (univariate) and well-being (multivariate, MR) were significantly associated with placebo response. Common side effects reported were insomnia (79%), anorexia (53%), nausea (38%) and restlessness (34%). MR analysis showed that worse baseline (ESAS) sleep, appetite, nausea, and restless are associated with increased reporting of these side effects ( Table ). Conclusions: Nearly half of advanced cancer patients enrolled in the fatigue trials responded to placebo. Worse physical well-being score was associated with placebo response. Patients experiencing specific symptoms at baseline were more likely to report these as side effects of the medication. These findings should be considered in fatigue clinical trial design. [Table: see text] No significant financial relationships to disclose.

scholarly journals Placebo and nocebo effects in the neurological practice

2015 ◽  
Vol 73 (1) ◽  
pp. 58-63 ◽  
Author(s):  
Caroline Bittar ◽  
Osvaldo J.M. Nascimento
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Gold Standard ◽  
Neurological Diseases ◽  
Nocebo Effect ◽  
Double Blind ◽  
Positive Effects ◽  
Specific Effects ◽  
Randomized Clinical Study ◽  
Nocebo Effects

Knowledge of placebo and nocebo effects is essential to identify their influence on the results in clinical practice and clinical trials, and thereby properly interpret their results. It is known that the gold standard of clinical trials research is the double-blind, placebo-controlled, randomized clinical study. The objective of this review is to distinguish specific from non-specific effects, so that the presence of positive effects in the group that received placebo (placebo effect) and the presence of adverse effects in the group receiving placebo (nocebo effect) lead to confounding in interpreting the results. Placebo and nocebo effects have been considered in neurological diseases such as depression, pain, headache, multiple sclerosis, epilepsy. As placebo and nocebo effects are also present in clinical practice, the purpose of this review is to draw attention to their influence on neurological practice, calling attention to the development of measures that can minimize them.

scholarly journals WHAT EVERY PSYCHOLOGIST AND PSYCHOTHERAPIST SHOULD KNOW ABOUT THE PLACEBO AND NOCEBO EFFECT

2021 ◽  
pp. 68-82
Author(s):  
Salvatore Giacomuzzi ◽  
Markus Ertl ◽  
Natalia Barinova ◽  
Klaus Garber ◽  
Alexander Kocharian
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Healthcare Professionals ◽  
Scientific Literature ◽  
Nocebo Effect ◽  
Positive Interaction ◽  
Ongoing Debate ◽  
Scientific Terminology ◽  
Medical Terms ◽  
Nocebo Effects

Purpose. Only a few medical terms are used as often, even in a metaphorically way, as the words placebo and nocebo. Almost any psychologist and psychotherapist think he/she knows well what by a placebo or nocebo is understood, but usually without really being able to explain it exactly and how it works. In addition, most psychologists and psychotherapists immediately think of clinical trials. However, many things are attributed to the placebo or nocebo effect that does not really fall under this concept in terms of a strict scientific terminology. Therefore, the following article summarizes the ongoing debate on placebo/nocebo effects by citing the current scientific literature. Methods. To realize the purpose of the study, we used the methods of theoretical scientific research. Results. In summary patients are more prone to develop nocebo effects are those with alternative or negative healthcare beliefs or experiences or unrealistic perceptions about treatment; managing these factors is a core strategy to counteract the nocebo effect. Conclusions. Healthcare professionals can help to minimise the influence of the nocebo effect by considering how information about treatments, including benefits and adverse effects, is framed and communicated. Establishing a positive interaction from the start and involving patients in decisions about their treatment and ensuring they understand the cause of their illness and what they can do to manage their symptoms is likely to lead to better treatment outcomes.

scholarly journals The Placebo and Nocebo Responses in Clinical Trials in Inflammatory Bowel Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Paul Enck ◽  
Sibylle Klosterhalfen
Keyword(s):  
Clinical Trials ◽  
Inflammatory Bowel Diseases ◽  
Placebo Response ◽  
Gastrointestinal Diseases ◽  
Nocebo Effect ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Maintenance Of Remission ◽  
Irritable Bowel ◽  
Meta Analyses

Placebo and nocebo responses are mostly discussed in clinical trials with functional bowel disorders. Much less has been investigated and is known in gastrointestinal diseases beyond irritable bowel syndrome (IBS), especially in inflammatory bowel diseases (IBD). For the purpose of this review, we screened the Journal of Interdisciplinary Placebo Studies (JIPS) database with approximately 4,500 genuine placebo research articles and identified nine meta-analyses covering more than 135 randomized and placebo-controlled trials (RCTs) with more than 10,000 patients with Crohn´s disease (CD) and another five meta-analyses with 150 RCTs and more than 10,000 patients with ulcerative colitis (UC). Only three discussed nocebo effects, especially in the context of clinical use of biosimilars to treat inflammation. The articles were critically analyzed with respect to the size of the placebo response in CD and UC, its effects on clinical improvement versus maintenance of remission, and mediators and moderators of the response identified. Finally, we discussed and compared the differences and similarities of the placebo responses in IBD and IBS and the nocebo effect in switching from biologics to biosimilars in IBD management.

scholarly journals Vitamin C in the Treatment of COVID-19

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1172
Author(s):  
Gregorio Paolo Milani ◽  
Marina Macchi ◽  
Anat Guz-Mark
Keyword(s):  
Clinical Trials ◽  
Vitamin C ◽  
Respiratory Infections ◽  
Medical Condition ◽  
Case Reports ◽  
Case Series ◽  
Theoretical Background ◽  
Current Evidence ◽  
Vitamin C Supplementation ◽  
Essential Nutrient

Vitamin C is an essential nutrient that serves as antioxidant and plays a major role as co-factor and modulator of various pathways of the immune system. Its therapeutic effect during infections has been a matter of debate, with conflicting results in studies of respiratory infections and in critically ill patients. This comprehensive review aimed to summarize the current evidence regarding the use of vitamin C in the prevention or treatment of patients with SARS-CoV2 infection, based on available publications between January 2020 and February 2021. Overall, 21 publications were included in this review, consisting of case-reports and case-series, observational studies, and some clinical trials. In many of the publications, data were incomplete, and in most clinical trials the results are still pending. No studies regarding prevention of COVID-19 with vitamin C supplementation were found. Although some clinical observations reported improved medical condition of patients with COVID-19 treated with vitamin C, available data from controlled studies are scarce and inconclusive. Based on the theoretical background presented in this article, and some preliminary encouraging studies, the role of vitamin C in the treatment of patients with SARS-CoV-2 infection should be further investigated.

scholarly journals Effects of open-label placebos in clinical trials: a systematic review and meta-analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Melina von Wernsdorff ◽  
Martin Loef ◽  
Brunna Tuschen-Caffier ◽  
Stefan Schmidt
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Medical Condition ◽  
Data Extraction ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Open Label ◽  
Cancer Related Fatigue ◽  
Promising Treatment ◽  
Irritable Bowel

AbstractOpen-label placebos (OLPs) are placebos without deception in the sense that patients know that they are receiving a placebo. The objective of our study is to systematically review and analyze the effect of OLPs in comparison to no treatment in clinical trials. A systematic literature search was carried out in February 2020. Randomized controlled trials of any medical condition or mental disorder comparing OLPs to no treatment were included. Data extraction and risk of bias rating were independently assessed. 1246 records were screened and thirteen studies were included into the systematic review. Eleven trials were eligible for meta-analysis. These trials assessed effects of OLPs on back pain, cancer-related fatigue, attention deficit hyperactivity disorder, allergic rhinitis, major depression, irritable bowel syndrome and menopausal hot flushes. Risk of bias was moderate among all studies. We found a significant overall effect (standardized mean difference = 0.72, 95% Cl 0.39–1.05, p < 0.0001, I2 = 76%) of OLP. Thus, OLPs appear to be a promising treatment in different conditions but the respective research is in its infancy. More research is needed, especially with respect to different medical and mental disorders and instructions accompanying the OLP administration as well as the role of expectations and mindsets.

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