4.0 Introduction
What the did the patients knew and when did they know it?
4.1 Blinding
In an experimental study, it is desirable (but not always possible) to keep the information about the treatments hidden from the patients and anyone involved with evaluating the patient. This is known as "blinding" or "masking." Blinding prevents conscious or subconscious biases or expectations from influencing the outcome of the study.
There is always some individual who knows which patients get which treatments, such as the pharmacy that prepares the pills and placebos. This is perfectly fine as long as these individuals do not interact with the patients or evaluate the patients.
There is a bit of ambiguity with respect to who is blinded (Devereaux et al 2001). For example, a survey of 25 textbooks produced nine different definitions of "double blind." Therefore, you should avoid using these terms and focus instead on which individuals are blinded. If you are evaluating an article, look for evidence of blinding for the following groups:
- the patients themselves,
- clinicians who have substantial interactions with the patients,
- anyone who assesses outcomes in these patients, or
- anyone who collects data from these patients.
If only some of the above are unaware of the treatment, then the study is partially blinded.
4.1.1 The effect of blinding on the patient.
Blinding prevents the placebo effect from distorting the research results. The placebo effect is a product of "belief, expectancy, cognitive reinterpretation, and diversion of attention" that can lead to psychological and sometimes physiological improvements in situations where the treatment is known to have no effect, such as sugar pills (Beyerstein 1997).
Johnson (1997) lists three specific situations where the placebo effect is of particular concern: when enthusiasm by the patient or the doctor for the new procedure is strong, when outcomes are based on the patient's self-assessment (e.g. quality of life studies), and when the treatment is primarily for symptoms. The placebo effect is less critical for objective outcomes like survival.
A recent study showed that the placebo effect might be overstated in some contexts (Hrobjartsson and Gotzsche 2001). Some of the effects attributed to the placebo are perhaps caused instead by statistical artefacts like regression to the mean or by the tendency of some conditions to resolve spontaneously .
Even without a placebo effect, blinding would still be important to ensure uniform rates of compliance. You want to avoid a situation where a patient thinks "I'm in the placebo arm, so it's not really important whether I show up for my follow-up evaluation."
4.1.2 The effect of blinding on the investigators.
The value of blinding also extends to the research team, and should include anyone who interacts with the patients. In a clinical trial of treatments for multiple sclerosis, a pair of neurologists assessed the outcome of each patient (Noseworthy et al 1994). One neurologist was blinded to the treatment status and one was unblinded. The unblinded neurologist gave substantially lower ratings to patients in the placebo group, which would have led to falsely concluding that one of the treatments was effective.
Researchers can also influence the outcome through their attitudes and through their differential use of other medications (Schulz et al 2002).
Those who collect data through an interview might probe harder for some patients if they are not blinded. Gail (1996) describes an observational study where the people asking questions about smoking and other risk factors were unaware of when they were interviewing lung cancer patients or controls. Thus, the interviewers could not subconsciously prod more for smoking information among the lung cancer patients.
4.1.3 When blinding is impossible
Unfortunately, there are many situations where blinding is impossible. For example, if you are comparing oral versus rectal administration of a drug, that's pretty hard to conceal from the patient. In general, observational studies cannot be blinded, because the patient and/or their doctor selects the treatment group.
Surgical procedures are often difficult to completely blind. Nevertheless, Johnson (1997) suggests some partial steps at blinding that prevent some of the biases from creeping in. If two surgical procedures use different types of incisions, identical blood or iodine stained opaque dressings could be used to keep the patients unaware of which operation was performed. Also, although the surgeon cannot be blinded to the difference in surgery, those who evaluate the health of the patient after surgery could be kept unaware of the particular operation, so as to ensure that their evaluation of the patient is unbiased.
Even though the placebo may look the same, sometimes the doctor may infer which group a patient belongs to, perhaps through noting a characteristic set of side effects. If you are worried about this, ask the doctors to try to identify which treatment group they believe each patient belonged to. If the percentage of correct guesses is significantly larger than 50%, then the allocation scheme was not sufficiently blinded.
Although unblinded studies are considered less authoritative than blinded studies, you should not use blinding as a surrogate marker for the quality of the research (Schulz et al 2002). For example, Rupert Sheldrake conducted a survey of various journals and showed that blinding was used in 85% of all parapsychology research. But it would be a mistake to claim, as Dr. Sheldrake does, that
"Parapsychologists ... have been constantly subjected to intense scrutiny by skeptics, and this has made them more rigorous." http://www.parascope.com/en/articles/blindScience.htm
Blinding is just of many factors that combine to indicate a study's rigor and quality.
4.1.4 The problem with studies without blinding.
Two researchers have examined studies with and without blinding. These authors found that studies without blinding show an average bias of 11-17% (Schulz 1996; Colditz 1989). In other words, when an unblinded study was compared to a blinded study, the former study tended to estimate a treatment effect that was (on average) 11% to 17% higher than the latter.
Additional evidence of this problem appears in a meta-analysis of the effect of intermittent sunlight exposure and melanoma (Nelemans 1995). When nine studies without blinding were combined, they showed a odds ratio of 1.84 which was statistically significant (95% confidence interval 1.52 to 2.25). When the seven studies with blinding were combined, they showed a much smaller odds ratio (1.17, 95% confidence interval 0.98 to 1.39) which was not statistically significant. This is further evidence that unblinded studies are more likely to show statistical significance than blinded studies.
4.2 Placebo controlled studies
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Placebos: what to look for.
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4.3 Equipoise
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Equipoise: what to look for.
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