Editing Blinded experiment (section)

==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]] is a source of [[bias]]. Some degree of premature unblinding is common in blinded experiments.<ref>{{cite journal |last1=Bello |first1=Segun |last2=Moustgaard |first2=Helene |last3=Hróbjartsson |first3=Asbjørn |title=Unreported formal assessment of unblinding occurred in 4 of 10 randomized clinical trials, unreported loss of blinding in 1 of 10 trials |journal=Journal of Clinical Epidemiology |volume=81 |pages=42–50 |doi=10.1016/j.jclinepi.2016.08.002 |pmid=27555081 |issn=1878-5921 |year=2017 }}</ref> When a blind is imperfect, its success is judged on a [[spectrum]] with [[open-label trial|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 dilemma|false dichotomy]].<ref>{{cite journal |last1=Schulz |first1=Kenneth F. |last2=Grimes |first2=David A. |s2cid=11578262 |title=Blinding in randomised trials: hiding who got what |journal=Lancet |date=23 February 2002 |volume=359 |issue=9307 |pages=696–700 |doi=10.1016/S0140-6736(02)07816-9 |pmid=11879884 |issn=0140-6736}}</ref>

Success of blinding is assessed by questioning study participants about information that has been masked to them (e.g. did the participant 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 [[latent variable|cannot be measured directly]], but must be inferred from participants' responses, its measured value will depend on the [[choice modeling|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]].<ref name=Kolahi2009>{{cite journal |last1=Kolahi |first1=J |last2=Bang |first2=H |last3=Park |first3=J |title=Towards a proposal for assessment of blinding success in clinical trials: up-to-date review. |journal=Community Dentistry and Oral Epidemiology |date=December 2009 |volume=37 |issue=6 |pages=477–84 |doi=10.1111/j.1600-0528.2009.00494.x |pmid=19758415 |pmc=3044082 |issn=1600-0528}}</ref>

===Post-study unblinding===
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 and control groups|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.<ref>{{cite journal |vauthors=Dinnett EM, Mungall MM, Kent JA, Ronald ES, McIntyre KE, Anderson E, Gaw A |s2cid=36252366 |title=Unblinding of trial participants to their treatment allocation: lessons from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) |journal=Clin Trials |volume=2 |issue=3 |pages=254–259 |date=2005 |pmid=16279148 |doi=10.1191/1740774505cn089oa }}</ref>

===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]] 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.<ref>{{cite journal |last1=Quittell |first1=Lynne M. |title=The Scientific and Social Implications of Unblinding a Study Subject |journal=The American Journal of Bioethics |date=3 October 2018 |volume=18 |issue=10 |pages=71–73 |doi=10.1080/15265161.2018.1513589 |pmid=30339067 |s2cid=53014880 |issn=1526-5161}}</ref>

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.<ref>{{cite journal |last1=Double |first1=D. B. |title=Placebo mania. Placebo controlled trials are needed to provide data on effectiveness of active treatment. |journal=BMJ: British Medical Journal |date=19 October 1996 |volume=313 |issue=7063 |pages=1008–9 |pmid=8892442 |pmc=2352320 |issn=0959-8138 |doi=10.1136/bmj.313.7063.1008b }}</ref> However, side effects are not the only cause of unblinding; any perceptible difference between the treatment and control groups can contribute to premature unblinding.{{cn|date=March 2023}}

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.<ref>{{cite journal |last1=Rees |first1=Judy R. |last2=Wade |first2=Timothy J. |last3=Levy |first3=Deborah A. |last4=Colford |first4=John M. |last5=Hilton |first5=Joan F. |title=Changes in beliefs identify unblinding in randomized controlled trials: a method to meet CONSORT guidelines |journal=Contemporary Clinical Trials |date=February 2005 |volume=26 |issue=1 |pages=25–37 |doi=10.1016/j.cct.2004.11.020 |pmid=15837450 |url=https://digitalcommons.unmc.edu/coph_epidem_articles/87 |url-access=subscription }}</ref> 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.<ref>{{cite web |last1=Ledford |first1=Heidi |title=A question of Control |url=https://www.nature.com/magazine-assets/d41586-018-07351-8/d41586-018-07351-8.pdf |publisher=Nature Magazine |access-date=24 April 2019}}</ref> CONSORT standards and [[good clinical practice]] guidelines recommend the reporting of all premature unblinding.<ref name=":0">{{cite journal |last1=Moher |first1=David |last2=Altman |first2=Douglas G. |last3=Schulz |first3=Kenneth F. |title=CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials |journal=BMJ |date=24 March 2010 |volume=340 |pages=c332 |doi=10.1136/bmj.c332 |pmid=20332509 |pmc=2844940 |language=en |issn=0959-8138}}</ref><ref>{{cite web |title=E6(R2) Good Clinical Practice: Integrated Addendum to ICH E6(R1) Guidance for Industry |url=https://www.fda.gov/downloads/Drugs/Guidances/UCM464506.pdf#page=24 |archive-url=https://web.archive.org/web/20170202012038/http://www.fda.gov/downloads/Drugs/Guidances/UCM464506.pdf#page=24 |url-status=dead |archive-date=February 2, 2017 |website=fda.gov |access-date=21 April 2019|date = 2019-04-05}}</ref> In practice, unintentional unblinding is rarely reported.<ref name=Bello2014 />

===Significance===
Bias due to poor blinding tends to favor the experimental group, resulting in inflated effect size and risk of [[type I error|false positives]].<ref name=":0" /> Success or failure of blinding is rarely reported or measured; it is implicitly assumed that experiments reported as "blind" are truly blind.<ref name=Bello2014 /> 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 [[statistical significance|statistically significant]] result in the absence of any real difference between test groups when a study is sufficiently [[Power (statistics)|powered]] (i.e. statistical significance is not robust to bias). As such, many statistically significant results in [[randomized controlled trial]]s may be caused by error in blinding.<ref>{{cite journal |last1=Siegfried |first1=Tom |title=Odds are, it's wrong: Science fails to face the shortcomings of statistics |journal=Science News |date=2010 |volume=177 |issue=7 |pages=26–29 |doi=10.1002/scin.5591770721 |language=en |issn=1943-0930}}</ref> Some researchers have called for the mandatory assessment of blinding efficacy in clinical trials.<ref name=Kolahi2009 />