When drugs are being trialed for their effectiveness, there are typically several stages. Double-blind trials are seen as the most reliable type of study because they involve neither the participant nor the doctor knowing who has received what treatment. The aim of this is to minimize the placebo effect and minimize bias.
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How they work
In double-blind trials, the treatment patients have is unknown to both patients and doctors until after the study is concluded. This differs from other types of trials, such as simple blind trials where only the patients are unaware of the treatment they are receiving, whereas the doctors know.
Double-blind trials are a form of randomized trials and can be ‘upgraded’ to triple-blind trials, in which the statisticians or data clean-up personnel are also blind to treatments.
To be effective, it is generally recommended that double-blind trials include around 100-300 people. If treatments are highly effective, smaller numbers can be used but if only 30 or so patients are enrolled the study is unlikely to be beneficial.
The assignment of patients into treatments is typically done by computers, where the computer assigns each patient a code number and treatment group. The doctor and patients only know the code number to avoid bias, hence allowing the study to be double-blind.
Double-blind trials can come in different varieties. Double-blind, placebo-controlled studies involve no one knowing the treatment assignments to remove the chance of placebo effects. In a double-blind comparative trial, a new treatment is often compared to the standard drug. This allows researchers to compare an established drug to a new one to establish which one is more advantageous.
However, unlike double-blind, placebo-controlled trials, they are not very good at statistically evaluating if a treatment is effective overall.
Benefits of double-blind trials
Double-blind trials remove any power of suggestion, as no one involved knows the treatment patients receive. This means that doctors carrying out the study don’t know and can’t accidentally tip off participants. Similarly, the doctors not being aware of the treatments means they do not unconsciously bias their interpretation of the study results.
The main principle behind double-blind and randomized trials, as opposed to simple blind trials, is to avoid bias in the treatment or experimental set-up. For example, if researchers are aware of the different treatment groups are getting, they may avoid assigning more unwell patients to the treatment group. Therefore, any effect seen by the treatment may have been related to how unwell a patient was to start with, rather than the efficacy of the drug.
COVID-19 and double-blind trials
Double-blind trials are usually needed for drugs and treatments to get approval to be used in many countries. However, good, comprehensive double-blind trials take time and require many participants. This has been especially problematic during the COVID-19 pandemic, as the world searches for pharmaceutical treatment options to improve survival and for a vaccine to prevent the spread of this virus.
In terms of treatment, the antiviral nucleotide analog remdesivir has been tested in several double-blind trials. The results of these have been conflicting, with results from Europe suggesting remdesivir was linked to faster recovery compared to placebo.
However, results from Wuhan in China found no significant effect of remdesivir on the time to clinical improvement, mortality, or time until virus clearance.
Differences in these studies include sample size (1 059 compared to 236 participants) and how unwell patients in the study were, with patients in Wuhan being less ill. This illustrates the difficulty in comparing the results of such trials, and that the likely effect of the drug is an intermediate of the two studies.
Some candidates for a COVID-19 vaccine have been identified and moved to phase II trials, which often involve double-blind methods. However, these also need to be conducted over meaningful timeframes to ensure any initial differences between the control and the treatment groups last in the long term.
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