In a blind or blinded experiment, information which may influence the participants of the
experiment
An experiment is a procedure carried out to support or refute a hypothesis, or determine the efficacy or likelihood of something previously untried. Experiments provide insight into Causality, cause-and-effect by demonstrating what outcome oc ...
is withheld until after the experiment is complete. Good blinding can reduce or eliminate experimental
bias
Bias is a disproportionate weight ''in favor of'' or ''against'' an idea or thing, usually in a way that is closed-minded, prejudicial, or unfair. Biases can be innate or learned. People may develop biases for or against an individual, a group, ...
es that arise from a participants' expectations,
observer's effect on the participants,
observer bias Observer bias is one of the types of detection bias and is defined as any kind of systematic divergence from accurate facts during observation and the recording of data and information in studies. The definition can be further expanded upon to incl ...
,
confirmation bias
Confirmation bias is the tendency to search for, interpret, favor, and recall information in a way that confirms or supports one's prior beliefs or values. People display this bias when they select information that supports their views, ignoring ...
, and other sources. A blind can be imposed on any participant of an experiment, including subjects, researchers, technicians, data analysts, and evaluators. In some cases, while blinding would be useful, it is impossible or unethical. For example, it is not possible to blind a patient to their treatment in a physical therapy intervention. A good
clinical protocol
In natural and social science research, a protocol is most commonly a predefined procedural method in the design and implementation of an experiment. Protocols are written whenever it is desirable to standardize a laboratory method to ensure succe ...
ensures that blinding is as effective as possible within ethical and practical constraints.
During the course of an experiment, a participant becomes
unblinded if they deduce or otherwise obtain information that has been masked to them. For example, a patient who experiences a side effect may correctly guess their treatment, becoming unblinded. Unblinding is common in blinded experiments, particularly in pharmacological trials. In particular, trials on
pain medication
An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...
and
antidepressants
Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...
are poorly blinded. Unblinding that occurs before the conclusion of a study is a source of experimental error, as the bias that was eliminated by blinding is re-introduced. The
CONSORT __NOTOC__
Consort may refer to:
Music
* "The Consort" (Rufus Wainwright song), from the 2000 album ''Poses''
* Consort of instruments, term for instrumental ensembles
* Consort song (musical), a characteristic English song form, late 16th–earl ...
reporting guidelines recommend that all studies assess and report unblinding. In practice, very few studies do so.
Blinding is an important tool of the
scientific method
The scientific method is an empirical method for acquiring knowledge that has characterized the development of science since at least the 17th century (with notable practitioners in previous centuries; see the article history of scientific m ...
, and is used in many fields of research. In some fields, such as
medicine
Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care pract ...
, it is considered essential. In clinical research, a trial that is not a blinded trial is called an
open trial.
History
The first blind experiment was conducted by the
French Royal Commission on Animal Magnetism in 1784 to investigate the claims of
mesmerism
Animal magnetism, also known as mesmerism, was a protoscientific theory developed by German doctor Franz Mesmer in the 18th century in relation to what he claimed to be an invisible natural force (''Lebensmagnetismus'') possessed by all liv ...
as proposed by Charles d'Eslon, a former associate of
Franz Mesmer
Franz Anton Mesmer (; ; 23 May 1734 – 5 March 1815) was a German physician with an interest in astronomy. He theorised the existence of a natural energy transference occurring between all animated and inanimate objects; this he called " ani ...
. In the investigations, the researchers (physically) blindfolded mesmerists and asked them to identify objects that the experimenters had previously filled with "vital fluid". The subjects were unable to do so.
In 1817, the first blind experiment recorded to have occurred outside of a scientific setting compared the musical quality of a
Stradivarius
A Stradivarius is one of the violins, violas, cellos and other string instruments built by members of the Italian family Stradivari, particularly Antonio Stradivari (Latin: Antonius Stradivarius), during the 17th and 18th centuries. They are co ...
violin to one with a guitar-like design. A violinist played each instrument while a committee of scientists and musicians listened from another room so as to avoid prejudice.
An early example of a double-blind protocol was the Nuremberg salt test of 1835 performed by Friedrich Wilhelm von Hoven, Nuremberg's highest-ranking public health official,
as well as a close friend of
Friedrich Schiller
Johann Christoph Friedrich von Schiller (, short: ; 10 November 17599 May 1805) was a German playwright, poet, and philosopher. During the last seventeen years of his life (1788–1805), Schiller developed a productive, if complicated, friends ...
. This trial contested the effectiveness of
homeopathic
Homeopathy or homoeopathy is a pseudoscientific system of alternative medicine. It was conceived in 1796 by the German physician Samuel Hahnemann. Its practitioners, called homeopaths, believe that a substance that causes symptoms of a dise ...
dilution.
[
One early essay advocating the blinding of researchers came from ]Claude Bernard
Claude Bernard (; 12 July 1813 – 10 February 1878) was a French physiologist. Historian I. Bernard Cohen of Harvard University called Bernard "one of the greatest of all men of science". He originated the term '' milieu intérieur'', and the ...
in the latter half of the 19th century. Bernard recommended that the observer of an experiment should not have knowledge of the hypothesis being tested. This suggestion contrasted starkly with the prevalent Enlightenment-era attitude that scientific observation can only be objectively valid when undertaken by a well-educated, informed scientist. The first study recorded to have a blinded researcher was conducted in 1907 by W. H. R. Rivers and H. N. Webber to investigate the effects of caffeine. The need to blind researchers became widely recognized in the mid-20th century.
Background
Bias
A number of biases are present when a study is insufficiently blinded. Patient-reported outcomes can be different if the patient is not blinded to their treatment. Likewise, failure to blind researchers results in observer bias Observer bias is one of the types of detection bias and is defined as any kind of systematic divergence from accurate facts during observation and the recording of data and information in studies. The definition can be further expanded upon to incl ...
. Unblinded data analysts may favor an analysis that supports their existing beliefs (confirmation bias
Confirmation bias is the tendency to search for, interpret, favor, and recall information in a way that confirms or supports one's prior beliefs or values. People display this bias when they select information that supports their views, ignoring ...
). These biases are typically the result of subconscious influences, and are present even when study participants believe they are not influenced by them.
Terminology
In medical research, the terms ''single-blind'', ''double-blind'' and ''triple-blind'' are commonly used to describe blinding. These terms describe experiments in which (respectively) one, two, or three parties are blinded to some information. Most often, single-blind studies blind patients to their treatment allocation, double-blind studies blind both patients and researchers to treatment allocations, and triple-blinded studies blind patients, researcher, and some other third party (such as a monitoring committee) to treatment allocations. However, the meaning of these terms can vary from study to study.
CONSORT guidelines state that these terms should no longer be used because they are ambiguous. For instance, "double-blind" could mean that the data analysts and patients were blinded; or the patients and outcome assessors were blinded; or the patients and people offering the intervention were blinded, etc. The terms also fail to convey the information that was masked and the amount of unblinding that occurred. It is not sufficient to specify the number of parties that have been blinded. To describe an experiment's blinding, it is necessary to report ''who'' has been blinded to ''what'' information, and ''how well'' each blind succeeded.
Unblinding
''Unblinding'' occurs in a blinded experiment when information becomes available to one from whom it has been masked. In clinical studies, unblinding may occur unintentionally when a patient deduces their treatment group. Unblinding that occurs before the conclusion of an experiment
An experiment is a procedure carried out to support or refute a hypothesis, or determine the efficacy or likelihood of something previously untried. Experiments provide insight into Causality, cause-and-effect by demonstrating what outcome oc ...
is a source of bias
Bias is a disproportionate weight ''in favor of'' or ''against'' an idea or thing, usually in a way that is closed-minded, prejudicial, or unfair. Biases can be innate or learned. People may develop biases for or against an individual, a group, ...
. Some degree of premature unblinding is common in blinded experiments. When a blind is imperfect, its success is judged on a spectrum
A spectrum (plural ''spectra'' or ''spectrums'') is a condition that is not limited to a specific set of values but can vary, without gaps, across a continuum. The word was first used scientifically in optics to describe the rainbow of colors i ...
with no blind (or complete failure of blinding) on one end, perfect blinding on the other, and poor or good blinding between. Thus, the common view of studies as blinded or unblinded is an example of a false dichotomy
A false dilemma, also referred to as false dichotomy or false binary, is an informal fallacy based on a premise that erroneously limits what options are available. The source of the fallacy lies not in an invalid form of inference but in a false ...
.
Success of blinding is assessed by questioning study participants about information that has been masked to them (e.g. did you receive the drug or placebo
A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures.
In general ...
?). In a perfectly blinded experiment, the responses should be consistent with no knowledge of the masked information. However, if unblinding has occurred, the responses will indicate the degree of unblinding. Since unblinding cannot be measured directly, but must be inferred from participants' responses, its measured value will depend on the nature of the questions asked. As a result, it is not possible to measure unblinding in a way that is completely objective. Nonetheless, it is still possible to make informed judgments about the quality of a blind. Poorly blinded studies rank above unblinded studies and below well-blinded studies in the hierarchy of evidence
A hierarchy of evidence (or levels of evidence) is a heuristic used to rank the relative strength of results obtained from scientific research. There is broad agreement on the relative strength of large-scale, epidemiological studies. More than 80 ...
.
Post-study unblinding
Post-study unblinding is the release of masked data upon completion of a study. In clinical studies
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dieta ...
, post-study unblinding serves to inform subjects of their treatment allocation. Removing a blind upon completion of a study is never mandatory, but is typically performed as a courtesy to study participants. Unblinding that occurs after the conclusion of a study is not a source of bias, because data collection and analysis are both complete at this time.
Premature unblinding
Premature unblinding is any unblinding that occurs before the conclusion of a study. In contrast with post-study unblinding, premature unblinding is a source of bias. A code-break procedure A code-break procedure is a set of rules which determine when planned unblinding should occur in a blinded experiment
In a blind or blinded experiment, information which may influence the participants of the experiment is withheld until after the ...
dictates when a subject should be unblinded prematurely. A code-break procedure should only allow for unblinding in cases of emergency. Unblinding that occurs in compliance with code-break procedure is strictly documented and reported.
Premature unblinding may also occur when a participant infers from experimental conditions information that has been masked to them. A common cause for unblinding is the presence of side effects (or effects) in the treatment group. In pharmacological trials, premature unblinding can be reduced with the use of an active placebo An active placebo is a placebo that produces noticeable side effects that may convince the person being treated that they are receiving a legitimate treatment, rather than an ineffective placebo.
Nomenclature
According to a 1965 paper, the term " ...
, which conceals treatment allocation by ensuring the presence of side effects in both groups. However, side effects are not the only cause of unblinding; any perceptible difference between the treatment and control groups can contribute to premature unblinding.
A problem arises in the assessment of blinding because asking subjects to guess masked information may prompt them to try to infer that information. Researchers speculate that this may contribute to premature unblinding. Furthermore, it has been reported that some subjects of clinical trials attempt to determine if they have received an active treatment by gathering information on social media and message boards. While researchers counsel patients not to use social media to discuss clinical trials, their accounts are not monitored. This behavior is believed to be a source of unblinding. CONSORT standards and good clinical practice Good clinical practice (GCP) is an international quality standard, which governments can then transpose into regulations for clinical trials involving human subjects. GCP follows the International Council for Harmonisation of Technical Requirements ...
guidelines recommend the reporting of all premature unblinding. In practice, unintentional unblinding is rarely reported.
Significance
Bias due to poor blinding tends to favor the experimental group, resulting in inflated effect size and risk of false positives
A false positive is an error in binary classification in which a test result incorrectly indicates the presence of a condition (such as a disease when the disease is not present), while a false negative is the opposite error, where the test result ...
. Success or failure of blinding is rarely reported or measured; it is implicitly assumed that experiments reported as "blind" are truly blind. Critics have pointed out that without assessment and reporting, there is no way to know if a blind succeeded. This shortcoming is especially concerning given that even a small error in blinding can produce a statistically significant result in the absence of any real difference between test groups when a study is sufficiently powered (i.e. statistical significance is not robust to bias). As such, many statistically significant results in randomized controlled trial
A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical te ...
s may be caused by error in blinding. Some researchers have called for the mandatory assessment of blinding efficacy in clinical trials.
Applications
In medicine
Blinding is considered essential in medicine, but is often difficult to achieve. For example, it is difficult to compare surgical and non-surgical interventions in blind trials. In some cases, sham surgery
Sham surgery (placebo surgery) is a faked surgical intervention that omits the step thought to be therapeutically necessary.
In clinical trials of surgical interventions, sham surgery is an important scientific control. This is because it isolate ...
may be necessary for the blinding process. A good clinical protocol
In natural and social science research, a protocol is most commonly a predefined procedural method in the design and implementation of an experiment. Protocols are written whenever it is desirable to standardize a laboratory method to ensure succe ...
ensures that blinding is as effective as possible within ethical and practical constrains.
Studies of blinded pharmacological trials across widely varying domains find evidence of high levels of unblinding. Unblinding has been shown to affect both patients and clinicians. This evidence challenges the common assumption that blinding is highly effective in pharmacological trials. Unblinding has also been documented in clinical trials outside of pharmacology.
Pain
A 2018 meta-analysis
A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...
found that assessment of blinding was reported in only 23 out of 408 randomized controlled trials for chronic pain (5.6%). The study concluded upon analysis of pooled data that the overall quality of the blinding was poor, and the blinding was "not successful." Additionally, both pharmaceutical sponsorship and the presence of side effects were associated with lower rates of reporting assessment of blinding.
Depression
Studies have found evidence of extensive unblinding in antidepressant
Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...
trials: at least three-quarters of patients were able to correctly guess their treatment assignment. Unblinding also occurs in clinicians. Better blinding of patients and clinicians reduces effect size
In statistics, an effect size is a value measuring the strength of the relationship between two variables in a population, or a sample-based estimate of that quantity. It can refer to the value of a statistic calculated from a sample of data, the ...
. Researchers concluded that unblinding inflates effect size in antidepressant trials. Some researchers believe that antidepressants are not effective for the treatment of depression and only outperform placebos due to systematic error. These researchers argue that antidepressants are just active placebo An active placebo is a placebo that produces noticeable side effects that may convince the person being treated that they are receiving a legitimate treatment, rather than an ineffective placebo.
Nomenclature
According to a 1965 paper, the term " ...
s.
Acupuncture
While the possibility of blinded trials on acupuncture
Acupuncture is a form of alternative medicine and a component of traditional Chinese medicine (TCM) in which thin needles are inserted into the body. Acupuncture is a pseudoscience; the theories and practices of TCM are not based on scientif ...
is controversial, a 2003 review of 47 randomized controlled trial
A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical te ...
s found no fewer than four methods of blinding patients to acupuncture treatment: 1) superficial needling of true acupuncture points, 2) use of acupuncture points which are not indicated for the condition being treated, 3) insertion of needles outside of true acupuncture points, and 4) the use of placebo needles which are designed not to penetrate the skin. The authors concluded that there was "no clear association between type of sham intervention used and the results of the trials."
A 2018 study on acupuncture which used needles that did not penetrate the skin as a sham treatment found that 68% of patients and 83% of acupuncturists correctly identified their group allocation. The authors concluded that the blinding had failed, but that more advanced placebos may someday offer the possibility of well-blinded studies in acupuncture.
In physics
It is standard practice in physics to perform blinded data analysis. After data analysis is complete, one is allowed to unblind the data. A prior agreement to publish the data regardless of the results of the analysis may be made to prevent publication bias.
In social sciences
Social science research is particularly prone to observer bias Observer bias is one of the types of detection bias and is defined as any kind of systematic divergence from accurate facts during observation and the recording of data and information in studies. The definition can be further expanded upon to incl ...
, so it is important in these fields to properly blind the researchers. In some cases, while blind experiments would be useful, they are impractical or unethical. Blinded data analysis can reduce bias, but is rarely used in social science research.
In forensics
In a police photo lineup, an officer shows a group of photos to a witness and asks the witness to identify the individual who committed the crime. Since the officer is typically aware of who the suspect is, they may (subconsciously or consciously) influence the witness to choose the individual that they believe committed the crime. There is a growing movement in law enforcement to move to a blind procedure in which the officer who shows the photos to the witness does not know who the suspect is.
In music
Auditions for symphony orchestras take place behind a curtain so that the judges cannot see the performer. Blinding the judges to the gender of the performers has been shown to increase the hiring of women. Blind tests can also be used to compare the quality of musical instruments.
See also
* Allocation concealment In a randomized experiment, allocation concealment hides the sorting of trial participants into treatment groups so that this knowledge cannot be exploited. Adequate allocation concealment serves to prevent study participants from influencing treatm ...
* Black boxing
In science studies, the social process of blackboxing is based on the abstract notion of a black box. To cite Bruno Latour, blackboxing is "the way scientific and technical work is made invisible by its own success. When a machine runs efficientl ...
* Blind taste test
In marketing, a blind taste test is often used as a tool for companies to compare their brand to another brand. For example, the Pepsi Challenge is a famous taste test that has been run by Pepsi since 1975. Additionally, taste tests are sometime ...
* Jadad scale
The Jadad scale, sometimes known as Jadad scoring or the Oxford quality scoring system, is a procedure to independently assess the methodological quality of a clinical trial. It is named after Colombian physician Alex Jadad who in 1996 described a ...
* Metascience
Metascience (also known as meta-research) is the use of scientific methodology to study science itself. Metascience seeks to increase the quality of scientific research while reducing inefficiency. It is also known as "''research on research''" ...
* Royal Commission on Animal Magnetism
The Royal Commission on Animal Magnetism involved two entirely separate and independent French Royal Commissions, each appointed by Louis XVI in 1784, that were conducted simultaneously by a committee composed of four physicians from the Paris ...
References
{{DEFAULTSORT:Blind Experiment
Design of experiments
Clinical research
Scientific method
French inventions
Medical statistics