Bias is one of the greatest barriers to effective research, so double-blind study designs have become a core part of gold-standard trials.
This design blinds the researcher and the subject until the end of the trial, thereby preventing confirmation bias in either party.
Double blinding is particularly common in the pharmaceutical sector where patients are prone to placebo effects, but it’s equally crucial in psychiatry, physics, and other hard sciences.
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Double-Blind Study – In a Nutshell
Double-blind study designs have evolved enormously in recent years to meet the challenges of a range of different research applications. This piece will explore those challenges by outlining:
- How single, double, and triple blinds work.
- When unblinding is necessary for a double-blind study and how to develop a procedure for it.
- How to cope with bias in trials that can’t be blinded.
The better your blinds, the purer your research, but all studies present their difficulties. We’ll find out how to adapt to a range of sciences.
Definition: Double-blind study
The double-blind study design masks information from both researchers and subjects to reduce the odds of bias. It also avoids the Stanford Prison Experiment effect by preventing researchers from influencing the outcomes of their research, either consciously or unconsciously.1
Double-blind study outcomes are easier to duplicate—And replication is a core characteristic of any scientific evidence.
The double-blind study design has its standard processes, test items, and control groups, so it allows researchers to replicate and test the study when required.
Masking also reduces the chance of test subjects developing placebo and nocebo effects, while preventing researchers from consciously or unconsciously altering their participants’ perceptions.3
Even so, double-blind study procedures aren’t the zenith of masking. Trials can be triple or even quadruple-blind.
Types of blind studies
A typical double-blind study keeps pertinent information from the subject and the researcher who’s experimenting. It has limitations, so triple-blind studies have emerged to hide the assignment from one additional party: The researcher who’s assessing the data.
Single blinding keeps information from the participants alone, usually when a double-blind study is either impossible or unnecessary.
In single-blind studies, researchers and data analysts are fully equipped with all the data relating to their experiment. The research subjects are the only ones who are blinded.
This design is common in medical studies that are at risk of the placebo effect, such as the US Army Research Command’s trial of the Hantaan vaccine.4
Here, outcomes were relatively assured of objectivity, so a double-blind study was considered unnecessary. Only patients were blinded. Additional measures were used to prevent selection bias in researchers.
In a double-blind study, any information that could influence research participants and participants is withheld.
This design is common when clinicians are required to interact with their participants.
Example:
When AstraZeneca studied ACD1222’s efficacy in preventing COVID, unblinded researchers could have swayed the results of their trial for financial gain, so a double-blind study design was chosen.5
In triple-blind studies, the data scientist’s expectations and prejudices are cut out of the process, along with those of the researcher and participant.
This prevents “observer bias”, so it’s particularly common in observational studies like the 2007 ViNeuro trial for Parkinson’s disease. Triple masking can even influence other hard sciences like particle physics.
The software has emerged to make the masking process easier, but in general, the analytics professional works with data values that have their data labels removed.
The importance of a double-blind study
Blinding is crucial to the integrity of random assignment research because it maintains the internal validity of the study.
A double-blind study allows researchers to prove a cause-and-effect relationship by eliminating bias. Non-blinded studies can trigger participants to change their actions or report their experiences differently.
They can also lead to biased reporting and alter the way doctors perform disease assessments.
Bias can be both intentional and accidental, so pure motives aren’t enough. Double blinding protects the integrity of the researcher and lends weight to their results, providing a smoother peer review process.
Unblinding happens when treatment or allocation data is shared with a participant or researcher during a double-blind study. This can happen purposefully or accidentally, and in many cases, it’s extremely subtle.
Unblinding can be useful in an emergency, but barring medical necessity, it can destroy the integrity of the double-blind study, requiring researchers to start all over again with new participants.
In some circumstances, unblinding has an enormous benefit.
Example:
If a participant falls pregnant during a double-blind study, researchers may unblind them to protect the fetus from untested pharmaceuticals.
Partial unblinding is often used for interim analysis when researchers have reason to fear for the safety of patients. It’s a tentative way to assess results without terminating the double-blind study entirely, but it’s often a requisite first step to the termination.
Sometimes blinding is impossible. In acupuncture studies:
Example:
A toothpick is often used instead of an acupuncture needle. This leaves the participant’s blind intact but makes the researcher’s blind impossible.
Many behavioral trials make blinding impossible for all but the data analyst. When blinding can’t be achieved, other tools can be used to reduce bias.
In the open cluster TRIGGER trial, where bleeding made blinding impossible, researchers were given subjective ways to assess the severity of that bleeding.6
Other techniques include:
- Mislabeling the desired outcome to blind the researcher and participant.
- Relying on a blinded adjudication committee to assess the outcome.
- Relying on clinical evidence rather than patient-reported outcomes.
- Eliminating a placebo control group.
FAQs
Blind studies can be single, double, and triple-blinded.
A quadruple-blind study masks outcomes assessors as well as patients and researchers.
While a double-blind study can reduce the severity of the placebo effect, it can’t eliminate it.
Even the mere interaction between the patient and the researcher can have a positive placebo effect, so bias can only be limited. It cannot be eliminated.
Usually, the only double-blind study participant with access to this information is the person directing the trial. Doctors and patients are entirely masked.
Sources
1 Zimbardo, Philip G. “The Stanford Prison Experiment.” Prison EXP. Accessed February 1, 2023. https://www.prisonexp.org/.
2 Formplus Blog. “Double Blind Studies in Research: Types, Pros & Cons.” Formplus. July 27, 2022. https://www.formpl.us/blog/double-blind-studies.
3 Winchester Hospital. “Health Library: Double-blind, Placebo-controlled Study.” Accessed February 1, 2023. https://www.winchesterhospital.org/health-library/article?id=21849.
4 ClinicalTrials.gov. “A Single-Blind Study to Evaluate the Safety, Tolerability, and Immunogenicity of Hantaan Puumala Virus DNA Vaccine.” May 8, 2016. https://clinicaltrials.gov/ct2/show/NCT02776761.
5 ClinicalTrials.gov. “Phase III Double-Blind, Placebo-Controlled Study of AZD1222 for the Prevention of COVID-19 in Adults.” February 24, 2023. https://clinicaltrials.gov/ct2/show/NCT04516746.
6 Kahan, Brennan C., Suzie Cro, Caroline J. Doré, Daniel J Bratton, Sunita Rehal, Nick A. Maskell. Najib Rahman, and Vipul Jairath. “Reducing Bias in Open-Label Trials where Blinded Outcome Assessment is not Feasible: Strategies from Two Randomised Trials.” Trials 15, (2014): 456. https://pubmed.ncbi.nlm.nih.gov/25416527/.