Blinded experiment

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In a blind or blinded experiment, information which may influence the participants of the experiment is withheld (masked or blinded) until after the experiment is complete. Good blinding can reduce or eliminate experimental biases that arise from the placebo effect, the observer effect, confirmation bias, 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, is not possible to blind a patient to their treatment in a physical therapy intervention. A good clinical protocol ensures that blinding is as effective as possible within ethical and practical constrains.

During the course of an experiment, a participant becomes unblinded if they deduce or otherwise obtain information that has been masked to them. 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. Unblinding is common in blind experiments, and must be measured and reported. Meta-research has revealed high levels of unblinding in pharmacological trials. In particular, antidepressant trials are poorly blinded. Reporting guidelines recommend that all studies assess and report unblinding. In practice, very few studies assess unblinding.[1]

Blinding is an important tool of the scientific method, and is used in many fields of research. In some fields, such as medicine, it is considered essential.[2] In clinical research, a trial that in not blinded trial is called an open trial.

History[edit]

The first blind experiment was conducted by the French Academy of Sciences in 1784 to investigate the claims of mesmerism as proposed by Franz Mesmer. In the experiment, researcher 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 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.[3][4]

One early essay advocating the blinding of researchers came from Claude Bernard in the latter half of the 19th century.[vague] 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.[5] 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.[6] The need to blind researchers became widely recognized in the mid-20th century.[7]

Background[edit]

Bias[edit]

A number of biases are present when a study is insufficiently blinded. For example, a patient who is not blinded to their treatment is subject to the placebo effect.[8] Likewise, failure to blind researchers results in observer bias, in which the researchers may unconsciously or accidently influence the outcome of the experiment.[9] Unblinded data analysts may favor an analysis that supports their existing beliefs (confirmation bias). These biases are typically the result of subconscious influences, and are present even when study participants believe they are not influenced by them.[10]

Terminology[edit]

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.[11]

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 fails 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.[12]

Unblinding[edit]

Unblinding occurs in a blinded experiment when information becomes available to one from whom it has been masked. Unblinding that occurs before the conclusion of an experiment is a source of bias. In blinded experiments, some degree of premature unblinding is common.[13] When a blind is imperfect, its success is judged on a spectrum 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 or studies as blinded or unblinded is an example of a false dichotomy.[14]

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?). 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.[15]

Post-study unblinding[edit]

Post-study unblinding is the release of masked data upon completion of a study. In clinical studies, 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.[16]

Premature unblinding[edit]

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 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.[17]

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, which conceals treatment allocation by ensuring the presence of side effects in both groups.[18] 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.[19] 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.[20] CONSORT standards and good clinical practice guidelines recommend the reporting of all premature unblinding.[21][22] In practice, unintentional unblinding is rarely reported.[1]

Significance[edit]

Bias due to poor blinding tends to favor the experimental group, resulting in inflated effect size and risk of false positives.[21] Success or failure of blinding is rarely reported or measured; it is implicitly assumed that experiments reported as "blind" are truly blind.[1] Critics have pointed out that without assessment and reporting, there is no way to know if a blind succeed. 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 trials may be caused by error in blinding.[23] Some researchers have called for the mandatory assessment of blinding efficacy in clinical trials.[15]

Applications[edit]

In medicine[edit]

Blinding is considered essential in medicine,[24] 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 may be necessary for the blinding process. A good clinical protocol 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 effect 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.[25]

Pain[edit]

A 2018 meta-analysis 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.[26]

Depression[edit]

Studies have found evidence of extensive unblinding in antidepressant trials: at least three quarters of patients are able to correctly guess their treatment assignment.[27] Unblinding also occurs in clinicians.[28] Better blinding of patients and clinicians reduces effect size. Researchers concluded that unblinding inflates effect size in antidepressant trials.[29][30][31] 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 placebos.[32][33]

Zinc[edit]

One clinical trial on the efficacy of zinc supplementation in the treatment of the common cold experienced failure of blinding due to the strong metallic after-taste of zinc.[34]

Acupuncture[edit]

While the possibility of blinded trials on acupuncture is controversial, a 2003 review of 47 randomized controlled trials 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."[35]

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.[36]

In physics[edit]

Modern nuclear physics and particle physics experiments often involve large numbers of data analysts working together to extract quantitative data from complex datasets. In particular, the analysts want to report accurate systematic error estimates for all of their measurements; this is difficult or impossible if one of the errors is observer bias. To remove this bias, the experimenters devise blind analysis techniques, where the experimental result is hidden from the analysts until they've agreed—based on properties of the data set other than the final value—that the analysis techniques are fixed.

One example of a blind analysis occurs in neutrino experiments, like the Sudbury Neutrino Observatory, where the experimenters wish to report the total number N of neutrinos seen. The experimenters have preexisting expectations about what this number should be, and these expectations must not be allowed to bias the analysis. Therefore, the experimenters are allowed to see an unknown fraction f of the dataset. They use these data to understand the backgrounds, signal-detection efficiencies, detector resolutions, etc.. However, since no one knows the "blinding fraction" f, no one has preexisting expectations about the meaningless neutrino count N' = N × f in the visible data; therefore, the analysis does not introduce any bias into the final number N which is reported. Another blinding scheme is used in B meson analyses in experiments like BaBar and CDF; here, the crucial experimental parameter is a correlation between certain particle energies and decay times—which require an extremely complex and painstaking analysis—and particle charge signs, which are fairly trivial to measure. Analysts are allowed to work with all the energy and decay data, but are forbidden from seeing the sign of the charge, and thus are unable to see the correlation (if any). At the end of the experiment, the correct charge signs are revealed; the analysis software is run once (with no subjective human intervention), and the resulting numbers are published. Searches for rare events, like electron neutrinos in MiniBooNE or proton decay in Super-Kamiokande, require a different class of blinding schemes.

The "hidden" part of the experiment—the fraction f for SNO, the charge-sign database for CDF—is usually called the "blindness box". At the end of the analysis period, one is allowed to "unblind the data" and "open the box".

In psychology[edit]

Psychology and social science research is particularly prone to observer bias, 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.

In forensics[edit]

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, he may (subconsciously or consciously) influence the witness to choose the individual that he believes 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.[37][38]

In music[edit]

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.[39]

See also[edit]

References[edit]

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