What to write
Who was blinded after assignment to interventions (eg, participants, care providers, outcome assessors, data analysts)
Examples
“Whereas patients and physicians allocated to the intervention group were aware of the allocated arm, outcome assessors and data analysts were kept blinded to the allocation.”1
“Blinding and equipoise were strictly maintained by emphasizing to intervention staff and participants that each diet adheres to healthy principles, and each is advocated by certain experts to be superior for long-term weight-loss. Except for the interventionists (dieticians and behavioural psychologists), investigators and staff were kept blind to diet assignment of the participants. The trial adhered to established procedures to maintain separation between staff that take outcome measurements and staff that deliver the intervention. Staff members who obtained outcome measurements were not informed of the diet group assignment. Intervention staff, dieticians and behavioural psychologists who delivered the intervention did not take outcome measurements. All investigators, staff, and participants were kept masked to outcome measurements and trial results.”2
“This was a double-blind study with limited access to the randomisation code . . . The treatment each patient received was not disclosed to the investigator, study site staff, patient, sponsor personnel involved with the conduct of the study (with the exception of the clinical supply staff and designated safety staff), or study vendors.”3
“Physicians, patients, nurses responsible for referring the patients, the statistician, also the investigators who rated the patients and administered the drugs, were all blinded to the allocation.”4
Explanation
The term “blinding” (masking) refers to withholding information about the assigned interventions from people involved in the trial who may potentially be influenced by this knowledge. Blinding is an important safeguard against bias, particularly when assessing subjective outcomes.5
Benjamin Franklin has been credited as being the first to use blinding in a scientific experiment.6 He blindfolded participants so they would not know when he was applying mesmerism (a popular healing technique of the 18th century) and in so doing demonstrated that mesmerism was a sham. Since then, the scientific community has widely recognised the power of blinding to reduce bias, and it has remained a commonly used strategy in scientific experiments.
The section on blinding terminology below defines the groups of individuals (ie, participants, healthcare providers, data collectors, outcome assessors, and data analysts) that can potentially introduce bias into a trial through knowledge of the treatment assignments. Participants may respond differently if they are aware of their treatment assignment (eg, respond more favourably when they receive the new treatment).5 Lack of blinding may also influence adherence with the intervention, use of co-interventions, and risk of dropping out of the trial.
Blinding terminology
For a technical term to be useful, its use and interpretation must be consistent. Authors of trials commonly use the term “double blind,” and less commonly the terms “single blind” or “triple blind.” A problem with this lexicon is that there is great variability in clinician interpretations and epidemiological textbook definitions of these terms.7 Moreover, a study of 200 randomised trials reported as double blind demonstrated 18 different combinations of groups actually blinded when the authors of these trials were surveyed, and approximately one in every five of these trials—reported as double blind—did not blind participants, healthcare providers, or data collectors.8
This research demonstrates that terms are ambiguous and, as such, authors and editors should abandon their usage in isolation without defining them. Authors should instead explicitly report the blinding status of the people involved for whom blinding may influence the validity of a trial.
The healthcare providers include all personnel (eg, physicians, chiropractors, physiotherapists, nurses) who care for the participants during the trial. Data collectors are the individuals who collect data on the trial outcomes. Outcome assessors are the individuals who determine whether a participant did experience the outcomes of interest.
Some researchers have also advocated blinding and reporting the blinding status of the data monitoring committee and the manuscript writers.9 Blinding of these groups is uncommon and the value of blinding them is debated.10
Sometimes one group of individuals (eg, the healthcare providers) is also the same individuals fulfilling another role in a trial (eg, the data collectors). Even if this is the case, the authors should state the blinding status of these groups to allow readers to judge the validity of the trial.
Unblinded healthcare providers may introduce similar biases; and unblinded data collectors may differentially assess outcomes (eg, frequency or timing), repeat measurements of abnormal findings, or provide encouragement during performance testing. Unblinded outcome assessors may differentially assess subjective outcomes, and unblinded data analysts may introduce bias through the choice of analytical strategies, such as the selection of favourable time points or outcomes and by decisions to remove patients from the analyses. These biases have been well documented.5,9,11–1314
Blinding, unlike allocation concealment (item 18), may not always be appropriate or possible. In pragmatic trials (trials that try to make the experience as close as real life so as to understand real world effectiveness), blinding of participants and healthcare providers would decrease the pragmatism of the trials, since patients in real life are not blinded.15 An example where blinding is impossible is a trial comparing levels of pain associated with sampling blood from the ear or thumb.16 However, in randomised trials for which blinding is possible, lack of blinding has usually been associated with empirical evidence of exaggeration in treatment effect estimates.175,18–22 Blinding is particularly important when outcome measures involve some subjectivity, such as assessment of pain. Yet, blinding may not be as important in certain fields or with certain outcomes. For example, blinding of data collectors and outcome assessors is unlikely to matter for objective outcomes, such as death from any cause. Indeed, some methodological investigations have not found that lack of blinding is associated with empirical evidence of bias in treatment effect estimates.2324–29 Even then, however, lack of participant or healthcare provider blinding can lead to other problems, such as differential attrition.30 In certain trials, especially surgical trials, blinding of participants and healthcare providers is often difficult or impossible, but blinding of data collectors and outcome assessors for both benefits and harms is often achievable and recommended. For example, lesions can be photographed before and after treatment and assessed by an external observer.31 Regardless of whether blinding is possible, authors can and should always state who was blinded (ie, participants, healthcare providers, data collectors, data analysts, and/or outcome assessors).32,33
However, authors frequently do not report whether blinding was used.34,35 For example, reports of 51% of 506 trials in cystic fibrosis,36 33% of 196 trials in rheumatoid arthritis,37 and 38% of 68 trials in dermatology38 did not state whether blinding was used. Similarly, a more recent review found that the reports of 38% of 622 trials in high impact anaesthesiology journals did not explicitly describe the trial as blinded or non-blinded.39 Moreover, when describing some form of blinding, the most used term was the ambiguous “double blind.”39 Authors should explicitly state who was blinded, but only 14% of 622 trials explicitly reported whether the three key groups of individuals—that is, the participants, healthcare providers, and data collectors—were blinded or not.39 The rate did improve from 10% to 26% over the years of that review, but more improvement is needed. Until authors of trials improve their reporting of blinding, readers will have difficulty in judging its adequacy.
The term “masking” is sometimes used in preference to “blinding” to avoid confusion with the medical condition of being without sight. However, “blinding” in its methodological sense appears to be more universally understood worldwide and to be generally preferred for reporting clinical trials.30,31,40
Training
The UK EQUATOR Centre runs training on how to write using reporting guidelines.
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