Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT04387851 |
Other study ID # |
META-BLOM-DD-2022 |
Secondary ID |
|
Status |
Completed |
Phase |
|
First received |
|
Last updated |
|
Start date |
March 1, 2019 |
Est. completion date |
December 1, 2021 |
Study information
Verified date |
January 2022 |
Source |
Leiden University Medical Center |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial Summary
Placebo and nocebo effects are defined as the positive and negative effects occurring after
the (supposed) administration of an inert treatment, which, through a given learning process,
is believed to have positive or negative effects. The objective of this study is to summarize
the available knowledge on experimental inductions of placebo and nocebo effects on
somatosensory sensations, specifically pain and itch. The aim isto investigate the extent to
which learning processes (such as conditioning and verbal suggestions) induce placebo and
nocebo effects on pain and itch in healthy humans. The researchers intent to examine
expectancy induction methods for placebo and nocebo effects on somatosensory sensations,
describe methodological attributes of the research and propose practical and theoretical
implications as well as future directions for research investigating placebo and nocebo
effects on somatosensory sensations.
Description:
Research questions include:
1. What is the average magnitude of placebo or nocebo effects on pain and on itch, across
included studies?
2. Across studies that tested multiple learning processes for placebo and nocebo effects on
pain, is the magnitude of a placebo or nocebo effect on pain different based on the
learning process used to induce the effect?
3. Does the magnitude of placebo or nocebo effects differ between the sensations of pain
and itch?
4. Are nocebo effects on pain and itch stronger than placebo effects on pain and itch, as
measured by their relative magnitude?
Dependent upon search results, the researchers intend to answer questions 1 and 2 with
meta-analysis, and questions 3 and 4 with systematic review.
Search Strategy:
PubMed, PsycINFO, EMBASE, and the Cochrane CENTRAL Methodology Library will be searched.
Languages are restricted to English, Dutch, and German. Publication period is not restricted.
Searches were initially conducted on March 18th, 2019. The detailed key-worded search
strategy will not be made publicly available until this review is complete.
Condition or domain being studied:
Experimental induction of placebo or nocebo effects on somatosensory sensations (i.e., pain
and/or itch). For the purposes of in- and exclusion, studies are considered to have induced a
placebo or nocebo effect if the (supposed) administration of an inert treatment, is paired
with a given learning process attempt to induce positive or negative outcome-effects
Participants/population:
Healthy, adult human volunteers. Patient samples will not be included to improve homogeneity
of the results.
Data extraction:
Titles and abstracts of articles retrieved using the search strategy and those from
additional sources will be screened by two independent reviewers to identify studies that
potentially meet the inclusion criteria outlined above. The full text of these articles and
articles about which doubts exist based on the title and/or abstract will be retrieved and
assessed for eligibility by two independent reviewers. Full texts that are considered to be
possibly eligible for inclusion or about which doubts exist will also be assessed for
eligibility by a third reviewer. Two independent reviewers will use a standardized form to
extract data from the included studies to derive study characteristics, assess study quality,
and for data analysis. Extracted information will include details of the intervention,
control condition, study population, sensation type and how sensations were measured (e.g.
self-report), type of experimental induction (i.e., learning method used), type of expectancy
(i.e., placebo or nocebo), information for quality assessment, and outcome data for
meta-analysis (e.g., sample size, mean, and standard deviation). Doubts regarding
data-extraction will be resolved through discussion with a second review author. Missing data
will be requested from the study authors.
Risk of bias assessment:
Risk of bias will be assessed using the method developed by Marcuzzi and colleagues in 2013
specifically for quantitative sensory testing studies. This method assesses 1) whether the
sample was clearly described, 2) whether the sample is representative of the population, 3)
whether the somatosensory assessment methods are standardized, validated, and well described,
4) adequate blinding if relevant, and 5) whether potential confounders were taken into
account.
Strategy for data synthesis:
A quantitative synthesis, using aggregate data, of the data is planned. The (standardized)
mean difference (with a 95% confidence interval) will be calculated for all included studies
for which sufficient data are available. Both between and within subject designs will be
included; sensitivity analyses will be conducted to test for a difference in design type
(within/between). If significant differences are detected, design type will be included in
the analyses as a moderator variable). Subsequently, the pooled effects for each of the
experimental induction will be analyzed using a random-effects model. The effects of
experimental inductions will also be compared between placebo and nocebo effects. If
sufficient data are available, the effects of the experimental inductions will be compared
between different somatosensory sensations (see below). Where statistical pooling is not
possible, the findings of the systematic review will be presented in narrative form.
Heterogeneity will be assessed with the I2 statistic, by visual inspection of the forest
plot(s), and by subset analyses (see below). The presence of publication bias will also be
assessed (e.g., via inspection of a funnel plot).