The Importance of Randomized Control Trials

Alana Dopp

April 24, 2020

There are 418 global clinical trials focused on COVID-19 treatments with 113 in the United States and 11 in Minnesota all trying to determine an effective treatment for the 2,182,734 global confirmed cases with 651 confirmed cases in Hennepin County alone.

While the results of these studies are often discussed on the news, it can be difficult to understand if a drug is truly successful in treating COVID-19. To provide clarification on these studies, I will discuss the strengths and weaknesses of two common study designs, randomized control trials and compassionate use studies.

Randomized control trials are the gold standard and the most commonly used study design for COVID-19 clinical trials. In randomized control trials, there are qualities that participants must have called inclusion and exclusion criteria. This includes having a certain set of symptoms like a fever or cough and being of a certain age, race or sex. These participants are then randomly divided into an experimental group that will receive a treatment and a control group. These groups are then followed to measure an outcome such as the amount of time it takes to recover from a disease. The figure below illustrates this process.

Due to the randomization of participants, the relationship between the treatment and outcome can be studied. The randomization reduces the effects of bias and the effects of lifestyle choices like smoking, physical activity and diet. The ability to study the relationship between the treatment and outcome is the major strength of randomized control trials.

There are however many weaknesses of randomized control trials. Due to the criteria that participants must meet, the study’s results can only be applied to people that have the same characteristics. This is referred to as a limited generalizability. Additionally, these studies are expensive and can be seen as unethical. The ethical concern of this study design is that a treatment could save lives while the placebo group dies. Due to these weaknesses, compassionate use studies have been a popular design for COVID-19 trials.

Compassionate use studies give a treatment to a patient who is not eligible to participate in a clinical trial and has a serious or life-threatening illness. A recent compassionate use study showed that 68% of patients with COVID-19 had clinical improvement with the use of remdesivir.

While these results seem promising, it is important to note that since this is not a randomized control trial the relationship between remdesivir and clinical improvement is affected by bias and external factors including but not limited to the severity of symptoms, prior treatments received and preexisting health conditions.

Compassionate use studies can be viewed as easier to conduct and more ethical since all patients in the study are eligible to receive treatment and one does not need to spend time and money planning a randomized control trial. Although randomized control trials can be viewed as unethical and expensive, there is a need to see data from well-conducted randomized control trials to establish a relationship between a drug and an improvement in symptoms among patients with COVID-19.

Luckily, the number of randomized control trials continues to grow globally with participation from local hospitals such as the University of Minnesota Medical Center, Hennepin County Medical Center and Regions Hospital. It will be important to follow the results of these studies while critically appraising the research findings. I am hopeful that these studies will find a treatment for patients with COVID-19.