Clinical trials are essential for testing new treatments and drugs. There are several different types of clinical trials that researchers can use depending on their objectives and the treatment being examined. One such type is a double blind study.
Also known as a double blinded study, this is a type of clinical trial where neither the participants or the doctors know who is receiving a particular treatment or placebo. Only those directing the study will know which participant is receiving which treatment.
Double blind studies are useful for a variety of different reasons, including the prevention of bias. We’ll walk you through everything there is to know about double blind experiments and how they are conducted.
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Origins of the double-blind study
One of the earliest recorded examples of a double blinded study was conducted in 1835 by Friedrich Willhelm von Hoven, a government health official in Bavaria, Germany. At the time, homeopathic drugs had become popular, especially among affluent households. Von Hoven wanted to test whether these drugs were a legitimate form of medicine.
Along with a ‘society of truth-loving men’, the study was designed and a widely publicized invitation sent out to anyone who was interested. The minimum number of participants was set at 50 and over 120 citizens met in a local tavern to sign up. After the trial was explained, 100 vials were numbered, shuffled and randomly split into two lots of 50. One half was filled with distilled snow water, and the other with ordinary salt in a homeopathic C30-dilution of distilled snow water.
The results of the study found that the vast majority of those who received the homeopathic salt dilution did not experience any ‘effect’, concluding that homeopathy was not a legitimate form of medicine.
When are double blind studies used?
Double blind studies can be used for any clinical trial where preventing bias is highly important, for example due to demand characteristics or the placebo effect. They are typically used to confirm the effectiveness of a drug, monitor its side effects, compare it to commonly used treatments, and collect information that will enable it to be used safely - all without potential bias.
Researchers might opt to use a double blind study design for a couple of reasons. Firstly, the participants don’t know which group they will be in, so their beliefs about the treatment are unlikely to influence the results. Secondly, researchers are not aware of who is receiving the real treatment, so they are less likely to accidentally reveal subtle hints that could influence the trial outcome.
Double blinding is commonly used during the second and third phases of a clinical trial, particularly the third phase. This phase is where a larger number of participants is used to gather more reliable data on the new treatment. The key objective is to continue learning more about the drug’s safety and efficacy, while ensuring it works better than already-available alternatives.
Phase three clinical trials are often required for regulatory approval. The FDA relies on the data from these types of trials to make informed decisions about the safety and approval of a new treatment or drug.
Why are double blind trials so important?
The double blind design aims to minimize or completely eliminate bias. This is key for testing new drugs, treatments, or therapies and ensuring reliable results. Double blind trials involve both control and experimental groups, enabling researchers to accurately compare the effects of the treatment versus the placebo or standard treatment.
The result of this is reliable and valid results that are free from the influence of placebo effects or researcher bias which can completely invalidate a clinical trial. Double blind studies also heavily contribute to the advancement of medical science and help to inform regulatory approvals for new treatments, particularly for the FDA.
Benefits of a double blind trial
Double blind studies offer several different benefits, both to researchers and participants. These types of studies can also largely benefit the general population as they ensure the efficacy of treatments and allow for accurate assessments of side effects. The key benefit though, is that double blind trials reduce the risk of a drug not actually working due to intended or unintended biases.
Reduced placebo effect
Many double blind trials are also placebo-controlled, which means one group receives the new treatment and the other receives a placebo. This often results in a reduced or non-existent placebo effect. Additionally, participant behavior can sometimes be influenced by their beliefs or preconceptions about the treatment they are receiving. This can unfortunately impact the outcome of the trial, which makes the double blind method essential for controlling behavioral biases.
What is the placebo effect?
The placebo effect is a phenomenon in which participants experience a perceived or actual improvement in their condition, even though they have received a non-active or ‘dummy’ treatment.
It can manifest itself as either or both physical and mental health improvements, depending on the treatment being examined. The physical response often mimics the effects of the actual treatment, triggering real physiological changes in the body. The psychological response usually stems from the patient’s expectations of improvement.
Why does a double blind trial reduce the placebo effect?
By opting for a control group (those that receive a placebo) and an experimental group in a double blind study, researchers can objectively assess the true efficacy of the new treatment more effectively. By ensuring both the participants and the researchers are unaware of who receives which treatment, influences can be minimized. This makes sure that any observed effects are due to the treatment itself, not psychological expectations.
Reduced researcher bias
Double blind studies can prevent researchers from unconsciously influencing the results of the trial. Sometimes, researchers treat patients differently based on their knowledge of who is receiving which treatment, which can be both intentional or accidental.
One example of researcher bias is unconscious influence. This is where researchers, when aware of who is receiving the actual treatment, could unconsciously offer positive expectations or subtle hints to participants. This may then influence participant responses and the interpretation of results.
Another example is consistency in treatment administration. In a double blind trial, all participants receive the same care and attention, regardless of the group they are in. This helps to maintain the integrity and validity of the trial results. Without knowing who is receiving which treatment, researchers may also collect data more objectively. This enables them to focus solely on measurable outcomes as opposed to personal expectations.
Reduced participant bias
Double blind studies help to reduce participant bias significantly. Without double blinding, some participants could have preconceived ideas about the impact of a drug or treatment. This could influence what the participant reports or presents as a result of receiving the new treatment - this is what is known as participant bias.
There can also be issues in clinical trials with expectation vs reality without the double blinding method. When a participant knows what treatment they are going to receive and already have an idea about the psychological effects they might experience, they could report improvements based on these expectations and not as a result of the treatment. Double blinding helps to isolate the treatment or drug’s true effects from psychological influences.
In a double blind experiment, participants are also more likely to provide unbiased feedback on their symptoms and side effects because they do not have preconceived expectations ahead of the treatment. This feedback is extremely valuable and leads to more reliable data being recorded.
Ensures the efficacy of treatments
Clinical trials fundamentally aim to ensure the efficacy and safety of new treatments or drugs. Double blind trials help to accurately determine whether a new treatment is effective by eliminating bias. These types of trials can more reliably attribute patient improvements or side effects to the treatment itself, as opposed to potential external factors or a placebo effect.
Double blind trials are vital for regulatory approval. The results form the basis for regulatory bodies to evaluate and approve new treatments, ensuring they are both effective and safe for public use or consumption.
Allows accurate assessment of side effects
Just as double blind trials ensure there is no participant bias in terms of symptom improvements or effects, they can also help to assess any potential side effects or safety concerns more reliably. When neither the participant or researcher know who has received which treatment, any noted side effects can be more confidently linked to the treatment or drug, instead of external factors.
Double blinding is also important for establishing accuracy in long-term side effects. For a drug or treatment to be deemed as effective and safe, both immediate and long-term side effects need to be recorded and monitored. This is more reliably achieved with double blinding because participants are more likely to be forthcoming with recording their side effects without preconceived biases.
Methods used to ensure a double blind trial is successful
Like any type of trial, it’s important to ensure a double blind study is designed and delivered to gain the most accurate results for success. There are several important steps needed for this to happen.
Create identical looking treatments and placebos
For a double blind study to be effective, both the active treatment and placebo must be as identical as possible. This means ensuring they look, taste and feel the same, without of course having the same medicinal properties. Ensuring this happens could involve matching the packaging, taste, texture, and physical appearance of the active treatment and placebo, for example in terms of size, color and shape.
This part of clinical trial design is vital in a blind experiment. Successfully carrying out this step ensures that neither the participants or healthcare professionals administering them can distinguish between the two treatments, therefore ensuring the elimination of potential biases.
Blinded administration of treatment
The second step in ensuring double blind trials are effective is in the administration of the treatments. Both the placebo and active treatment should be administered so that neither the participant or the person administering them knows which is which. To do this, experiments might use color coded containers or have separate teams preparing each of the doses.
Randomized numbering systems
Randomization is an important element in many different clinical trials, especially double blind studies. It’s used to ensure participants given a particular treatment are given it randomly, and not because of any external factors. Randomization in clinical trials is often conducted using computer algorithms that generate unpredictable sequences, ensuring the assignment of treatment or placebo is not biased and completely random.
For example, each participant would receive a unique code that corresponds to either the treatment or the placebo. The coding system would only be known to an independent third party and not revealed until the study is complete and results accurately collected.
Use of third-party services
Third-party services are frequently used in clinical trials, for a variety of reasons. In double blind studies, researchers might use any number of third parties, such as organizations for delivering the treatment, software companies for randomized number allocation, or manufacturers for creating containers or the medications themselves.
To further distance the research team from any potential clues as to which participants have been given which treatments, third-party organizations are often involved in the preparation and distribution of the treatment and placebo. This means any administration bias is completely removed and the collected results will be more reliable.
When selecting third parties in a clinical study, there is often a set criteria that researchers must use. This could include a proven track record in maintaining confidentiality, and experience in clinical trial logistics. It could also even include experience in the type of treatment or drug being administered.
Standardizing procedures and interactions
A key reason why double blind trials work so well is that everything is standardized. This means, there is no special treatment for either the active drug group or the placebo group. The treatments are administered in the same way, the same dosage is given, and monitoring and its frequency is the same.
Interactions with participants are the same across the board too. This means clinicians are often scripted in terms of what they say to participants and how they interact with them. The reason for this is to avoid accidentally giving away which group the participant is in.
Training staff
Staff training is vital in all clinical trials, but particularly double blind studies. Any staff members involved in a clinical trial must undergo training to ensure they do not accidentally reveal which treatment a participant is receiving. They will learn how they should interact with participants, what they can and cannot say, and even how to control body language.
If a double blind clinical trial involves code breaking, which means a randomized code is broken either at the very end of the study or in the best interest of a participant, responsible healthcare professionals would be given additional training. While training is given before a trial begins, staff and participant behavior is also monitored throughout the trial to prevent any cues or biases that could affect the outcome of the trial or lead to unblinding.
Regular monitoring for premature unblinding
Premature unblinding is when the blinding element of the trial is inadvertently or intentionally broken before the trial is complete. When this happens, it’s possible that the entire clinical study would be invalidated. This would not only be a disappointment for medical research but can also be very costly.
To ensure the success of a double blind study, certain processes and procedures must be in place to eradicate any potential premature unblinding. Throughout the blinding period, it’s important that only pre-identified and trained staff have access to the treatment information to avoid any bias breaches. Researchers also typically use monitoring methods to avoid premature unblinding in the form of internal audits, blind spot checks, and regular reviews of trial conduct.
If premature unblinding does occur, the clinical study team will follow the protocols set out at the beginning of the trial. These could include any number of different steps depending on the severity of the unblinding and range from retraining staff and adjusting protocols to discarding compromised data or abandoning the trial completely.
Double blind study examples
The double blind technique has been used in medical research for a long time, and it continues to be a valid and important type of clinical trial. Since its conception, double blinding has been used in many life changing studies and drug trials.
Polio vaccine trials (1950s)
By the 1950s, polio had killed several hundreds of thousands, including children. As such, several vaccines were being developed to treat children who contracted polio, including a vaccine by Dr. Jonas Salk. The polio vaccine field trials of 1954 are among the largest double blind clinical trials ever completed, with over 623,000 school-age children injected with either the vaccine or placebo.
The results of this clinical study were announced in 1955, showing good statistical evidence that this vaccine was 80-90% effective in the prevention of polio. Following this, the polio vaccine was widely adopted and has since gone on to nearly eradicate polio around the world.
The HIV/AIDS antiretroviral trials
The HIV/AIDS epidemic in the 1980s and 1990s was a wide scale medical emergency, with several pharmaceutical companies and medical professionals racing to find a treatment or cure. In the early 1990s, double blind clinical trials took place to test the efficacy of antiretroviral drugs in treating HIV/AIDS as the existing treatment options were already becoming ineffective.
The success of this double blind trial marked a significant turning point in the fight against HIV/AIDS. Effective antiretroviral therapy (ART) was developed, transforming HIV/AIDS from a fatal diagnosis to a manageable chronic condition.
Double blind vs single and triple blind studies
Double blind studies are just one level of blinding in a study, clinical researchers can also opt for single or triple blinding. While double blinding is the most popular of the three levels, each has a place in clinical research depending on the circumstances and requirements of the trial in question.
Single blinding vs double blinding
Single blinding in a trial is where participants do not know which study group they are in, but researchers do. This is in contrast to double blind studies where neither group knows who receives which treatment.
The problem with single blinding is that the study’s conduct or results could be influenced by the researchers knowing which participants have been given which treatment. Single blind studies are often used in experiments where double blinding is impractical or impossible.
Double blinding vs triple blinding
Triple blinding in a clinical trial is another step up from double blinding, where the participants and researchers are blinded, as well as the data analysts, data collectors, and outcome adjudicators. The high level of objectivity in this type of trial means that bias for or against the active treatment is very unlikely to occur.
A triple blind element is not always practical or needed in a clinical trial. The increased complexity and resource requirements can be difficult to manage, making this level of blinding highly impractical. In most cases, researchers would opt for double blinding over triple blinding, still ensuring the trial is robust and reliable.
Conclusion
When it comes to blinding in clinical trials, double blinding is one of the most commonly used methods, and for good reason. The key benefit of double blinding is that it’s highly effective at preventing bias, which is critical for collecting accurate and reliable study data. In addition, double blinding is relatively easy and practical to incorporate in a study design.
If you’re looking for a clinical study to join, or you’re educating yourself on various types of clinical trials before you delve into the research landscape, understanding how double blinding works is essential.